subject:(electron transport chain)

Dalhousie University

1. Gawryluk, Ryan. Comparative Proteomics: Studies on the Composition and Evolution of the Mitochondrial Proteome in Eukaryotic Microbes (Protists).

Degree: PhD, Department of Biochemistry & Molecular Biology, 2011, Dalhousie University

URL: http://hdl.handle.net/10222/14078

► Mitochondria are eukaryotic organelles derived in evolution from within the ? subdivision of Proteobacteria. Although mitochondria are structurally and metabolically complex, modern-day mitochondrial genomes (mtDNA)… (more)

▼ Mitochondria are eukaryotic organelles derived in evolution from within the ? subdivision of Proteobacteria. Although mitochondria are structurally and metabolically complex, modern-day mitochondrial genomes (mtDNA) encode only a small number of RNAs and proteins predominantly involved in adenosine triphosphate (ATP) formation through electron transport coupled to oxidative phosphorylation, as well as translation of mtDNA-encoded proteins. In humans, only 13 of the >1000 polypeptides that constitute the complete mitochondrial protein complement (proteome) are encoded in mtDNA; the remainder is encoded by nuclear DNA (nuDNA). It is therefore imperative to comprehensively catalog nuDNA-encoded mitochondrial proteins in order to understand holistically the evolution of mitochondria. Mitochondrial proteome investigations of animals, fungi and land plants have dramatically altered our conception of mitochondrial evolution: in contrast to mtDNA-encoded proteins, few nuDNA-encoded mitochondrial proteins are demonstrably derived from the eubacterial progenitor of mitochondria, and many are found only in eukaryotes. Notably, however, little is known about the mitochondria of eukaryotic microbes (protists), which constitute the bulk of biochemical and genetic diversity within the domain Eucarya. The proteomic characterization of protist mitochondria is therefore crucial to fully elucidating mitochondrial function and evolution. Employing tandem mass spectrometry (MS/MS), I have analyzed highly purified mitochondria from Acanthamoeba castellanii (Amoebozoa). In combination, nearly 750 nuDNA- and mtDNA-encoded proteins were identified. These data were used to catalog metabolic pathways and protein complexes, and to infer functional and evolutionary profiles of A. castellanii mitochondria. My analyses suggest that while A. castellanii mitochondria have many features in common with other eukaryotes, they possess several novel attributes and pronounced metabolic versatility. An analysis of the A. castellanii electron transport chain (ETC) was also performed, utilizing a combination of blue native polyacrylamide gel electrophoresis (BN-PAGE), MS/MS and bioinformatic queries. A significant proportion of A. castellanii ETC proteins was identified, yielding several insights into ETC evolution in eukaryotes. Lastly, I present two unusual cases of ‘split’ mitochondrial proteins: the iron-sulfur subunit SdhB of succinate:ubiquinone oxidoreductase (Complex II), in the phylum Euglenozoa and Cox1 of cytochrome c:O2 oxidoreductase (Complex IV) in various eukaryotes, including A. castellanii. Functional and evolutionary implications of these findings are discussed. Advisors/Committee Members: Bernard Lemire (external-examiner), Richard Singer (graduate-coordinator), John Archibald (thesis-reader), Jan Rainey (thesis-reader), Andrew Roger (thesis-reader), Michael W. Gray (thesis-supervisor), Not Applicable (ethics-approval), Yes (manuscripts), Yes (copyright-release).

Subjects/Keywords: mitochondria; evolution; proteomics; electron transport chain; protist

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APA (6^th Edition):

Gawryluk, R. (2011). Comparative Proteomics: Studies on the Composition and Evolution of the Mitochondrial Proteome in Eukaryotic Microbes (Protists). (Doctoral Dissertation). Dalhousie University. Retrieved from http://hdl.handle.net/10222/14078

Chicago Manual of Style (16^th Edition):

Gawryluk, Ryan. “Comparative Proteomics: Studies on the Composition and Evolution of the Mitochondrial Proteome in Eukaryotic Microbes (Protists).” 2011. Doctoral Dissertation, Dalhousie University. Accessed April 14, 2021. http://hdl.handle.net/10222/14078.

MLA Handbook (7^th Edition):

Gawryluk, Ryan. “Comparative Proteomics: Studies on the Composition and Evolution of the Mitochondrial Proteome in Eukaryotic Microbes (Protists).” 2011. Web. 14 Apr 2021.

Vancouver:

Gawryluk R. Comparative Proteomics: Studies on the Composition and Evolution of the Mitochondrial Proteome in Eukaryotic Microbes (Protists). [Internet] [Doctoral dissertation]. Dalhousie University; 2011. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10222/14078.

Council of Science Editors:

Gawryluk R. Comparative Proteomics: Studies on the Composition and Evolution of the Mitochondrial Proteome in Eukaryotic Microbes (Protists). [Doctoral Dissertation]. Dalhousie University; 2011. Available from: http://hdl.handle.net/10222/14078

University of Iowa

2. Kloepping, Kyle Christohper. Mitochondria-targeted therapy for metastatic melanoma.

Degree: PhD, Free Radical and Radiation Biology, 2015, University of Iowa

URL: https://ir.uiowa.edu/etd/5958

► Melanoma incidence is increasing faster than any other cancer in the world today. Disease detected early can be cured by surgery, but once melanoma… (more)

▼ Melanoma incidence is increasing faster than any other cancer in the world today. Disease detected early can be cured by surgery, but once melanoma progresses to the metastatic stage it is lethal, with an overall median survival of less than one year. The poor prognosis for late stage melanoma patients is attributed to the intrinsic resistance of melanoma to all Federal Drug Administration approved melanoma therapies. Therefore, there is a critical need for novel treatment approaches that circumvent melanoma therapy resistance. Emerging evidence suggests that differences in melanoma metabolism relative to non-malignant cells represents a potential target for therapeutic intervention. The research presented here demonstrates the potential for using triphenylphosphonium-based compounds as a new therapeutic platform for metastatic melanoma that is designed to take advantage of these metabolic differences. In vitro experiments demonstrate that triphenylphosphonium-based compounds modified with an aliphatic side chain target melanoma cell mitochondria and promote melanoma cell death via mitochondria metabolism inhibition and subsequent reactive oxygen species production. Increased reactive oxygen species production results in decreased glutathione levels and an oxidized cellular state. There is also a structure-activity relationship between side chain length, metabolic disruption, and melanoma cell cytotoxicity. Further, results demonstrate that traditional in vivo triphenylphosphonium drug administration routes such as oral gavage, intraperitoneal injection, and intravenous injection do not result in significant tumor accumulation of triphenylphosphonium drugs. However, the use of a thermosensitive hydrogel delivery system localizes triphenylphosphonium drugs directly at the melanoma tumor site and decreases melanoma tumor growth rate. These results suggest that a hydrogel-based triphenlyphosphonium delivery system could potentially be a therapeutic strategy that circumvents melanoma resistance mechanisms in order to provide durable therapy for an increasing number of metastatic melanoma patients worldwide. Advisors/Committee Members: Schultz, Michael K. (supervisor).

Subjects/Keywords: Electron Transport Chain; Hydrogel; Melanoma; Metabolism; Mitochondria; Triphenylphosphonium

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APA (6^th Edition):

Kloepping, K. C. (2015). Mitochondria-targeted therapy for metastatic melanoma. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/5958

Chicago Manual of Style (16^th Edition):

Kloepping, Kyle Christohper. “Mitochondria-targeted therapy for metastatic melanoma.” 2015. Doctoral Dissertation, University of Iowa. Accessed April 14, 2021. https://ir.uiowa.edu/etd/5958.

MLA Handbook (7^th Edition):

Kloepping, Kyle Christohper. “Mitochondria-targeted therapy for metastatic melanoma.” 2015. Web. 14 Apr 2021.

Vancouver:

Kloepping KC. Mitochondria-targeted therapy for metastatic melanoma. [Internet] [Doctoral dissertation]. University of Iowa; 2015. [cited 2021 Apr 14]. Available from: https://ir.uiowa.edu/etd/5958.

Council of Science Editors:

Kloepping KC. Mitochondria-targeted therapy for metastatic melanoma. [Doctoral Dissertation]. University of Iowa; 2015. Available from: https://ir.uiowa.edu/etd/5958

University of South Florida

3. Siegel, Sasha Victoria. Mitochondrial Heteroplasmy Contributes to the Dynamic Atovaquone Resistance Response in Plasmodium falciparum.

Degree: 2016, University of South Florida

URL: https://scholarcommons.usf.edu/etd/6586

► Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant… (more)

▼ Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant hurdle to progress worldwide. Atovaquone is used in combination with proguanil (Malarone) as an antimalarial treatment in uncomplicated malaria, but is rendered ineffective by the rapid development of atovaquone resistance during treatment. Previous studies have established that de novo mutant parasites confer resistance to atovaquone with a substitution in amino acid 268 in the cytochrome b gene encoded by the parasite mitochondrial genome, yet much is still unknown about how this resistance develops, and whether parasites are inherently predisposed to resistance development. Here we report phenotypic characterization of isolates from patients that failed treatment in the original atovaquone Phase II studies in Thailand by using a diverse series of chemotypes that target mitochondrial functions. We defined their structure-activity relationships and observed broad resistance (5-30,000 fold in atovaquone), suggesting that cytochrome b mutations alone are not sufficient to explain this spectrum of resistance. We also report the first known in vitro selection that recapitulates the clinical Y268S mutation using the TM90-C2A genetic background, the pre-treatment parent for TM90-C2B. Selection of the Y268S mutation in TM90-C2A and others indicates that the parasite genetic background is critical in the selection of clinical atovaquone resistance, since selection attempts in multiple other genetic backgrounds results in mutations at positions other than amino acid 268. We implicate mitochondrial heteroplasmy in the development of sporadic, rapid resistance to atovaquone, where pre-existing low-level mutations in the multi-copy mitochondrial DNA can be quickly selected for in parasite populations. High-coverage mitochondrial deep-sequencing data showed that low-level Y268S mutants were present in admission parasites from the atovaquone Phase II clinical trials in Thailand, and recrudescent parasites either maintained high level Y268S mutation frequencies or gradually returned to cryptic Y268S levels. The phenomenon of gradual heteroplasmic conversion back to wild-type was noted in some ex vivo patient isolated parasites as well as some in vitro selected lines, which suggests that other factors are at play that influence heteroplasmy stability. In addition to mitochondrial heteroplasmy, the total mtDNA copy number is likely influencing phenotypes in a gene dose-dependent fashion. Further, pressure on the DHODH enzyme that results in DHODH copy number amplifications/mutations has been shown to influence mitochondrial heteroplasmy directly. Last, mitochondrial diversity was shown to be vastly underestimated without heteroplasmic loci being taken into account, as seen in the re-analysis of the Pf3K MalariaGEN genome dataset we performed. The complex interactions between these drug resistance mechanisms reveal the phenotypic and genotypic…

Subjects/Keywords: Malaria; Electron Transport Chain; Drug Resistance; Bioinformatics; Molecular Biology; Parasitology

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APA (6^th Edition):

Siegel, S. V. (2016). Mitochondrial Heteroplasmy Contributes to the Dynamic Atovaquone Resistance Response in Plasmodium falciparum. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/6586

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Siegel, Sasha Victoria. “Mitochondrial Heteroplasmy Contributes to the Dynamic Atovaquone Resistance Response in Plasmodium falciparum.” 2016. Thesis, University of South Florida. Accessed April 14, 2021. https://scholarcommons.usf.edu/etd/6586.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Siegel, Sasha Victoria. “Mitochondrial Heteroplasmy Contributes to the Dynamic Atovaquone Resistance Response in Plasmodium falciparum.” 2016. Web. 14 Apr 2021.

Vancouver:

Siegel SV. Mitochondrial Heteroplasmy Contributes to the Dynamic Atovaquone Resistance Response in Plasmodium falciparum. [Internet] [Thesis]. University of South Florida; 2016. [cited 2021 Apr 14]. Available from: https://scholarcommons.usf.edu/etd/6586.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Siegel SV. Mitochondrial Heteroplasmy Contributes to the Dynamic Atovaquone Resistance Response in Plasmodium falciparum. [Thesis]. University of South Florida; 2016. Available from: https://scholarcommons.usf.edu/etd/6586

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Montana

4. Stump, Sascha Christian LaMotte. STRUCTURAL CHARACTERIZATION OF THE HUMAN C-MYC QUADRUPLEX AND MECHANISTIC EVALUATION OF ANTITUMOR AGENTS: ANTHRACENYL ISOXAZOLE AMIDES AND QUINOLINEDIONES.

Degree: PhD, 2018, University of Montana

URL: https://scholarworks.umt.edu/etd/11292

► Cancer is a disease characterized by the abnormal proliferation of cells in the body. For many forms of cancer, there remain only limited and… (more)

▼ Cancer is a disease characterized by the abnormal proliferation of cells in the body. For many forms of cancer, there remain only limited and often ineffective treatment options available. Treatment of cancer is problematic for several reasons that include the difficulty in establishing molecular targets, finding interventions that cause selective toxicity to cancer cells, and the uniform capability of cancer cells to evade apoptosis. To address this, new strategies must be employed that take advantage of novel mechanisms of action to develop better therapies. The goal of this research is to aid in this effort through the study of emerging targets and antitumor agents. In these studies, we characterize the structure of an important target in the field of anticancer drug design, the quadruplex formed in the human c-MYC promoter region. The oncogene c-MYC is dysregulated or overexpressed in approximately 70% of human cancers and contributes to many survival pathways used by cancer cells to evade apoptosis. Stabilization of the c-MYC promoter quadruplex has been shown to reduce c-MYC expression and cause apoptosis in tumor cells. We also examine the mechanisms of action of two novel classes of antitumor agents, the anthracenyl isoxazole amides (AIMs) and a group of 5,8-quinolinedione analogs. We demonstrate interactions of the AIMs with quadruplex-forming sequences found in human telomeres, the c-MYC promoter, and mitochondrial DNA. Additionally, we provide evidence that the AIMs can inhibit the electron transport chain of mitochondria, specifically Complex II. Further, we show that treatment with the AIMs causes damage to mitochondrial DNA and loss of the mitochondrial membrane potential, leading to the intrinsic pathway of apoptosis in human glioblastoma cells. We also show a novel set of 5,8-quinolinedione analogs have potent antitumor activity in human breast cancer cells not related to their suitability as substrates for the NQO1-reductase that is often overexpressed in cancer. Together, this work has provided new insights to the field of anticancer drug discovery through characterization of an important target, the c-MYC promoter quadruplex, and through analysis of two novel classes of antitumor compounds, the AIMs and the 5,8-quinolinediones.

Subjects/Keywords: antitumor; c-MYC; DNA; electron transport chain; mitochondria; quadruplex

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Stump, S. C. L. (2018). STRUCTURAL CHARACTERIZATION OF THE HUMAN C-MYC QUADRUPLEX AND MECHANISTIC EVALUATION OF ANTITUMOR AGENTS: ANTHRACENYL ISOXAZOLE AMIDES AND QUINOLINEDIONES. (Doctoral Dissertation). University of Montana. Retrieved from https://scholarworks.umt.edu/etd/11292

Chicago Manual of Style (16^th Edition):

Stump, Sascha Christian LaMotte. “STRUCTURAL CHARACTERIZATION OF THE HUMAN C-MYC QUADRUPLEX AND MECHANISTIC EVALUATION OF ANTITUMOR AGENTS: ANTHRACENYL ISOXAZOLE AMIDES AND QUINOLINEDIONES.” 2018. Doctoral Dissertation, University of Montana. Accessed April 14, 2021. https://scholarworks.umt.edu/etd/11292.

MLA Handbook (7^th Edition):

Stump, Sascha Christian LaMotte. “STRUCTURAL CHARACTERIZATION OF THE HUMAN C-MYC QUADRUPLEX AND MECHANISTIC EVALUATION OF ANTITUMOR AGENTS: ANTHRACENYL ISOXAZOLE AMIDES AND QUINOLINEDIONES.” 2018. Web. 14 Apr 2021.

Vancouver:

Stump SCL. STRUCTURAL CHARACTERIZATION OF THE HUMAN C-MYC QUADRUPLEX AND MECHANISTIC EVALUATION OF ANTITUMOR AGENTS: ANTHRACENYL ISOXAZOLE AMIDES AND QUINOLINEDIONES. [Internet] [Doctoral dissertation]. University of Montana; 2018. [cited 2021 Apr 14]. Available from: https://scholarworks.umt.edu/etd/11292.

Council of Science Editors:

Stump SCL. STRUCTURAL CHARACTERIZATION OF THE HUMAN C-MYC QUADRUPLEX AND MECHANISTIC EVALUATION OF ANTITUMOR AGENTS: ANTHRACENYL ISOXAZOLE AMIDES AND QUINOLINEDIONES. [Doctoral Dissertation]. University of Montana; 2018. Available from: https://scholarworks.umt.edu/etd/11292

NSYSU

5. Chu, Ling-ya. Reactive oxygen species generated by phenylarsine oxide facilitate neurotransmitter release at developing Xenopus neuromuscular synapse.

Degree: Master, Biological Sciences, 2012, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0629112-192559

► Phenylarsine oxide (PAO) is a membrane-permeable trivalent arsenic compounds, which interfere the biochemical activity of intracellular enzymes or proteins through reacting specifically with sulfhydryl and… (more)

▼ Phenylarsine oxide (PAO) is a membrane-permeable trivalent arsenic compounds, which interfere the biochemical activity of intracellular enzymes or proteins through reacting specifically with sulfhydryl and vicinal dithiol groups in the protein structure. Although the deleterious effects of arsenic compounds in bioorganisms have been extensively studied, however its role in the synaptogenesis is still obscure. Here we test the role of PAO on the synaptic activity at developing Xenopus neuromuscular synapse by using whole-cell patch clamp recording. Bath application of PAO dose-dependently increases the frequency of spontaneous synaptic currents (SSC frequency) and reaches its maximal effect at 10 Î¼M. The SSC frequency is robustly facilitated in 10~15 minutes after PAO application and then the release of neurotransmitter were abruptly ceased due to the degenerative collapse of the presynaptic motoneuron. Pretreatment of the culture with Ca2+ chelator BAPTA-AM significantly blunted the SSC frequency facilitation induced by PAO, suggesting a rise in Ca2+ in presynaptic motoneuron is a prerequisite. The PAO-induced SSC frequency facilitation is unaffected even that Ca2+ is eliminated from culture medium or addition of pharmacological Ca2+ channel inhibitor cadmium, indicating the influx of extracellular Ca2+ is not needed for the rise of [Ca2+]i. Depletion of endoplasmic reticulum Ca2+ pool with thapsigargin effectively hampered the PAO-induced SSC frequency facilitation. Pretreatment of ryanodine receptor inhibitor TMB-8 but not IP3 receptor inhibitor XeC significantly occluded the increase of SSC frequency elicited by PAO. Furthermore, bath application of the culture with either mitochondria oxidative phosphorylation uncoupler FCCP or mitochondrial permeability transition pore inhibitor cyclosporin A significantly abolished the SSC facilitating effect of PAO. Pretreatment the culture with TMB-8 and cyclosporin A have no addictive effects on the occlusion of PAO-induced SSC frequency facilitation, suggesting a consecutively released Ca2+ from internal store through ryanodine receptor and mitochondria is responsible for PAO-induced SSC frequency facilitation. The synaptic facilitating effect of PAO is eliminated while incubated with free radical scavenger n-acetylcysteine. Furthermore, treating cultures with complex III of electron transport chain (ETC) inhibitor antimycin A, but not complex I inhibitor rotenone, abolished PAO-induced facilitation of synaptic transmission. PAO elicited no facilitation effects on SSC frequency when pretreatment the culture with either thiol-modifying agent NEM or thiol-reducing agent DTT. Overall, results from our current study provide evidences that reactive oxygen species derived from PAO inhibition on complex III of ETC induce the open of MPT pore in mitochondria, the accompanied Ca2+ leak from mitochondria and Ca2+-induced Ca2+ release from endoplasmic reticulum resulted in a robustly release of neurotransmitter and a destructive damage on the neuron. Advisors/Committee Members: Chun-lin Chen (chair), Jau-cheng Liou (committee member), Bin-nan Wu (chair).

Subjects/Keywords: electron transport chain; Xenopus neuromuscular synapse; phenylarsine oxide; reactive oxygen species; mitochondrial permeability transition pore

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APA (6^th Edition):

Chu, L. (2012). Reactive oxygen species generated by phenylarsine oxide facilitate neurotransmitter release at developing Xenopus neuromuscular synapse. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0629112-192559

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chu, Ling-ya. “Reactive oxygen species generated by phenylarsine oxide facilitate neurotransmitter release at developing Xenopus neuromuscular synapse.” 2012. Thesis, NSYSU. Accessed April 14, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0629112-192559.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chu, Ling-ya. “Reactive oxygen species generated by phenylarsine oxide facilitate neurotransmitter release at developing Xenopus neuromuscular synapse.” 2012. Web. 14 Apr 2021.

Vancouver:

Chu L. Reactive oxygen species generated by phenylarsine oxide facilitate neurotransmitter release at developing Xenopus neuromuscular synapse. [Internet] [Thesis]. NSYSU; 2012. [cited 2021 Apr 14]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0629112-192559.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chu L. Reactive oxygen species generated by phenylarsine oxide facilitate neurotransmitter release at developing Xenopus neuromuscular synapse. [Thesis]. NSYSU; 2012. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0629112-192559

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Univerzitet u Beogradu

6. Golić, Igor Lj., 1981-. Molekulske osnove strukturnog remodeliranja mitohondrija indukovanog kalcijumom i insulinom u mrkim adipocitima pacova.

Degree: Biološki fakultet, 2016, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:10740/bdef:Content/get

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Biologija - Biologija ćelija i tkiva / Biology - Cell and Tissue Biology

Osnovna uloga mrkog masnog tkiva je održanje tjelesne temperature i održanje energetske… (more)

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Biologija - Biologija ćelija i tkiva / Biology - Cell and Tissue Biology

Osnovna uloga mrkog masnog tkiva je održanje tjelesne temperature i održanje energetske homeostaze organizma. Izlaganje hladnoći, a i povećan unos hrane, dovodi do stimulacije, proliferacije i diferencijacije mrkih adipocita, što je praćeno remodeliranjem mitohondrija, termogenih organela mrkih adipocita. U okviru strukturnog remodeliranja mitohondrije pokazuju širok dijapazon morfoloških promjena (broj mitohondrija u ćeliji, srednji dijametar, fuzija i fisija mitohondrija, volumenska gustina kristi) što je povezano sa prisustvom pojedinih kompleksa elektron transportnog lanca, ATP sintaze, familije UCP proteina, posebno UCP1, a i drugih proteina unutrašnje membrane mitohondrija. Kalcijum igra veoma važnu ulogu u termogenezi, njegova koncentracija u citoplazmi i organelama mrkih adipocita je hormonski regulisana, prije svega noradrenalinom. Mitohondrije, s jedne strane, imaju važnu ulogu u oblikovanju signalnih puteva kalcijuma, a kalcijum, s druge strane, u fiziološkim koncentracijama stimuliše mitohondrijalni metabolizam i povećava produkciju energije, dok u visokim koncentracijama indukuje apoptozu. Insulin je jedan od glavnih modulatora termogene funkcije mrkih adipocita, gdje stimuliše sintezu i deponovanje lipida u mrkim adipocitima, proliferaciju mrkih adipocita, angiogenezu i vazodilataciju. Pokazano je da insulin utiče na aktivnost elektron transportnog lanca, a i da mitohondrije pojačavaju insulinsku osjetljivost putem redoks regulacije proteina tirozin kinaze i insulinskog receptora. Cilj ove doktorske disertacije je rasvjetljavanje kako kalcijum, s jedne strane, a insulin, s druge strane, utiču na molekulske mehanizme koje su uključene u strukturno remodeliranje mitohondrija mrkih adipocita pacova. U eksperimentu su korišćeni Wistar pacovi, starosti dva mjeseca. U eksperimentu sa Ca-SANDOZ, životinje su podijeljene u dve grupe, jedna je pila Ca-SANDOZ rastvoren u vodi, a druga, kontrolna, česmensku vodu, tri dana. U eksperimentu sa insulinom, pacovi su podijeljeni u šest grupa, četiri grupe su primale nisku (0.4 IU) ili visoku (4 IU) dozu insulina i to jedan (akutno) ili tri dana (hronično). Ostale dvije grupe, kontrolne, su primale fiziološki rastvor akutno ili hronično. Trećeg dana tretmana Ca-SANDOZ, odnosno tri sata poslije posljednjeg tretmana insulinom, životinje su žrtvovane dekapitacijom, a interskapularni depo BAT je izolovan i pripremljen za biohemijske, mikroskopske i molekularno-biološke analize, i za izolaciju mitohondrijalnih frakcija. BAT i mitohondrijama bogata frakcija su analizirane Western Blot analizom, imunohistohemijskom, imunofluorescentnom i imunogold analizama, ultrastukturnim i stereološkim analizama, a analizirana je i aktivnost ATP sintaze...

Advisors/Committee Members: Korać, Aleksandra, 1964-.

Subjects/Keywords: mitochondria; brown adipocyte; insulin; calcium; ATP synthase; IF1; electron transport chain; UCP1; mitochondrial remodeling

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Golić, Igor Lj., 1. (2016). Molekulske osnove strukturnog remodeliranja mitohondrija indukovanog kalcijumom i insulinom u mrkim adipocitima pacova. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:10740/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Golić, Igor Lj., 1981-. “Molekulske osnove strukturnog remodeliranja mitohondrija indukovanog kalcijumom i insulinom u mrkim adipocitima pacova.” 2016. Thesis, Univerzitet u Beogradu. Accessed April 14, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:10740/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Golić, Igor Lj., 1981-. “Molekulske osnove strukturnog remodeliranja mitohondrija indukovanog kalcijumom i insulinom u mrkim adipocitima pacova.” 2016. Web. 14 Apr 2021.

Vancouver:

Golić, Igor Lj. 1. Molekulske osnove strukturnog remodeliranja mitohondrija indukovanog kalcijumom i insulinom u mrkim adipocitima pacova. [Internet] [Thesis]. Univerzitet u Beogradu; 2016. [cited 2021 Apr 14]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:10740/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Golić, Igor Lj. 1. Molekulske osnove strukturnog remodeliranja mitohondrija indukovanog kalcijumom i insulinom u mrkim adipocitima pacova. [Thesis]. Univerzitet u Beogradu; 2016. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:10740/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

NSYSU

7. Hsu, Yuan-ting. Signal derived from photosynthic electron transport regulates the expression of methionine sulfoxide reductase (Msr) gene in the green macroalga Ulva fasciata Delile.

Degree: PhD, Marine Biology, 2008, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1120108-183121

► This study has investigated the involvement of photosynthetic electron transport chain on the regulation of gene expression of methionine sulfoxide reductase (UfMSR) in the marine… (more)

Subjects/Keywords: DCMU; Ulva fasciata; methionine sulfoxide reductase; electron transport chain; Antimycin A; hydroxylamine; Light; stigmatellin; SHAM; DCPIP; DBMIB

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APA (6^th Edition):

Hsu, Y. (2008). Signal derived from photosynthic electron transport regulates the expression of methionine sulfoxide reductase (Msr) gene in the green macroalga Ulva fasciata Delile. (Doctoral Dissertation). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1120108-183121

Chicago Manual of Style (16^th Edition):

Hsu, Yuan-ting. “Signal derived from photosynthic electron transport regulates the expression of methionine sulfoxide reductase (Msr) gene in the green macroalga Ulva fasciata Delile.” 2008. Doctoral Dissertation, NSYSU. Accessed April 14, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1120108-183121.

MLA Handbook (7^th Edition):

Hsu, Yuan-ting. “Signal derived from photosynthic electron transport regulates the expression of methionine sulfoxide reductase (Msr) gene in the green macroalga Ulva fasciata Delile.” 2008. Web. 14 Apr 2021.

Vancouver:

Hsu Y. Signal derived from photosynthic electron transport regulates the expression of methionine sulfoxide reductase (Msr) gene in the green macroalga Ulva fasciata Delile. [Internet] [Doctoral dissertation]. NSYSU; 2008. [cited 2021 Apr 14]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1120108-183121.

Council of Science Editors:

Hsu Y. Signal derived from photosynthic electron transport regulates the expression of methionine sulfoxide reductase (Msr) gene in the green macroalga Ulva fasciata Delile. [Doctoral Dissertation]. NSYSU; 2008. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-1120108-183121

Penn State University

8. Song, Yanguang. Respiratory Pathways Used By Perchlorate¨CRespring Bacteria.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6234

► Systematic experiments were performed to examine the inhibitory effects of oxygen on perchlorate reduction and to identify the components and branches in the electron transport… (more)

▼ Systematic experiments were performed to examine the inhibitory effects of oxygen on perchlorate reduction and to identify the components and branches in the electron transport chains involved in perchlorate reduction and aerobic respiration by Dechlorosoma sp. KJ (ATCC strain BAA-592). To investigate the effect of dissolved oxygen (DO) on perchlorate reduction, anaerobically grown cultures of Dechlorosoma sp. KJ were exposed to near-saturated concentration of DO for various periods of time. It was determined that cells exposed to oxygen for more than 12 hours were incapable of reducing perchlorate. Cells exposed to oxygen for less than 12 hours, when re-introduced to anoxic conditions, quickly reduced the redox potential to highly negative values (-127 mV to -337 mV) and were able to reduce perchlorate or chlorite. This result suggested that aeration during backwashing of biofilm reactors, or exposure of perchlorate-degrading cell suspensions to oxygen for periods of less than 12 hours, will not be detrimental to the ability of perchlorate-degrading bacteria to use perchlorate as an electron acceptor. Inhibitors were used to block specific respiratory enzymes, and thus to identify elements of the electron transport chain (ETC) involved in the reduction of molecular oxygen and perchlorate (Chapters 3 and 4). Inhibition of dissimilative perchlorate reduction by a low concentration of cyanide was due to oxygen build up, not inhibition of enzymes used for perchlorate reduction. The threshold DO concentration to inhibit perchlorate reduction was < 0.04 mg/L. The main ETC used by cells grown on high DO concentrations likely contains cytochrome bc1, cytochrome c and cytochrome aa3. When cells were grown on perchlorate, DO uptake occurred via a shorter ETC than that used by cells grown at higher DO concentrations. The ETC to oxygen at low DO concentrations is branched off the quinone to cytochrome bd, while the ETC to perchlorate is branched off the quinone to perchlorate reductase. These results should be useful in helping to improve the design and operation of biological perchlorate treatment systems. Advisors/Committee Members: Bruce Ernest Logan, Committee Chair/Co-Chair, William D Burgos, Committee Member, John Michael Regan, Committee Member, Maryann Victoria Bruns, Committee Member.

Subjects/Keywords: perchlorate reduction; bioremediation; perchlorate; electron transport chain; redox potential

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APA (6^th Edition):

Song, Y. (2008). Respiratory Pathways Used By Perchlorate¨CRespring Bacteria. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6234

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Song, Yanguang. “Respiratory Pathways Used By Perchlorate¨CRespring Bacteria.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6234.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Song, Yanguang. “Respiratory Pathways Used By Perchlorate¨CRespring Bacteria.” 2008. Web. 14 Apr 2021.

Vancouver:

Song Y. Respiratory Pathways Used By Perchlorate¨CRespring Bacteria. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6234.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Song Y. Respiratory Pathways Used By Perchlorate¨CRespring Bacteria. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6234

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Univerzitet u Beogradu

9. Đorđević, Mirko S., 1986-. Evolucija starenja kod laboratorijskih populacija Acanthoscelides obtectus: uloga mitohondrija i oksidativnog stresa.

Degree: Biološki fakultet, 2017, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:15786/bdef:Content/get

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Biologija - Evoluciona biologija / Biology - Evolutionary biology

Ključna pretpostavka evolucione teorije starenja jeste da opadanje uzrasno-specifičnog preživljavanja organizama predstavlja rezultat smanjenja intenziteta prirodne… (more)

Subjects/Keywords: ageing; mitochondria; oxidative stress; mitonuclear interactions; electron transport chain; life history traits; laboratory evolution; Acanthoscelides obtectus

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APA (6^th Edition):

Đorđević, Mirko S., 1. (2017). Evolucija starenja kod laboratorijskih populacija Acanthoscelides obtectus: uloga mitohondrija i oksidativnog stresa. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:15786/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Đorđević, Mirko S., 1986-. “Evolucija starenja kod laboratorijskih populacija Acanthoscelides obtectus: uloga mitohondrija i oksidativnog stresa.” 2017. Thesis, Univerzitet u Beogradu. Accessed April 14, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:15786/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Đorđević, Mirko S., 1986-. “Evolucija starenja kod laboratorijskih populacija Acanthoscelides obtectus: uloga mitohondrija i oksidativnog stresa.” 2017. Web. 14 Apr 2021.

Vancouver:

Đorđević, Mirko S. 1. Evolucija starenja kod laboratorijskih populacija Acanthoscelides obtectus: uloga mitohondrija i oksidativnog stresa. [Internet] [Thesis]. Univerzitet u Beogradu; 2017. [cited 2021 Apr 14]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:15786/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Đorđević, Mirko S. 1. Evolucija starenja kod laboratorijskih populacija Acanthoscelides obtectus: uloga mitohondrija i oksidativnog stresa. [Thesis]. Univerzitet u Beogradu; 2017. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:15786/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

North-West University

10. Steenkamp, Anzaan. Establishing the comet assay to determine the effects of different perturbations on DNA repair capacity / by Anzaan Steenkamp .

Degree: 2011, North-West University

URL: http://hdl.handle.net/10394/4628

► Single cell gel electrophoresis (SCGE), more commonly known as the Comet assay, is an uncomplicated, affordable and versatile method for investigating DNA damage and repair.… (more)

▼ Single cell gel electrophoresis (SCGE), more commonly known as the Comet assay, is an uncomplicated, affordable and versatile method for investigating DNA damage and repair. Existing comet–assay based methods were modified and applied in this study in order to examine the effects of different perturbations on the DNA repair capacity of different samples. Mitochondrial functioning has a vast effect on overall cell physiology and does not simply involve the production of energy in the form of ATP that sustains common biological processes, but is also associated with important cellular occurrences such as apoptosis and ROS production. It is suggested that a change in mitochondrial function may lead to extensive ROS production which may negatively affect macromolecules, including proteins involved in DNA repair pathways, and impaired energy formation which in turn may hamper the proper occurrence of energy driven processes. Complex I and ?III knock–down systems established in 143B cells are used to investigate the effect that perturbations of the energy metabolism may have on DNA repair capacity. Metallothioneins (MTs) are known to play an imperative role in trace element homeostasis and detoxification of metals and are effective ROS scavengers. The prooxidant environment that heavy metal imbalance causes may result in mutagenesis and transformation through DNA damage. It is suggested that an imbalance in the metal homeostasis caused by MT knock–out may create an environment favourable for DNA damage formation and at the same time impair DNA repair pathways. Because of the multi–functionality and involvement of metallothioneins in such a wide variety of biological processes, it was considered interesting and essential to extend the investigation on the effect of the absence of metallothioneins on DNA repair. A metallothionein I and ?II knock–out mouse model is employed to determine the effect of MT knock–out on DNA repair capacity. It was clear from the results obtained that transfection of cells, as used to investigate a perturbation in the energy metabolism in 143B cells, has an impairing effect on DRC. It was also confirmed that metallothioneins play an important and diverse role in cell biology since the absence thereof inhibits both BER and NER.

Subjects/Keywords: Comet assay; DNA repair capacity; Base excision repair (BER); Nucleotide excision repair (NER); Electron transport chain; Metallothionein

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APA (6^th Edition):

Steenkamp, A. (2011). Establishing the comet assay to determine the effects of different perturbations on DNA repair capacity / by Anzaan Steenkamp . (Thesis). North-West University. Retrieved from http://hdl.handle.net/10394/4628

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Steenkamp, Anzaan. “Establishing the comet assay to determine the effects of different perturbations on DNA repair capacity / by Anzaan Steenkamp .” 2011. Thesis, North-West University. Accessed April 14, 2021. http://hdl.handle.net/10394/4628.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Steenkamp, Anzaan. “Establishing the comet assay to determine the effects of different perturbations on DNA repair capacity / by Anzaan Steenkamp .” 2011. Web. 14 Apr 2021.

Vancouver:

Steenkamp A. Establishing the comet assay to determine the effects of different perturbations on DNA repair capacity / by Anzaan Steenkamp . [Internet] [Thesis]. North-West University; 2011. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10394/4628.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Steenkamp A. Establishing the comet assay to determine the effects of different perturbations on DNA repair capacity / by Anzaan Steenkamp . [Thesis]. North-West University; 2011. Available from: http://hdl.handle.net/10394/4628

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign

11. Lencina, Andrea Mariana. Biochemical characterization of respiratory chain flavoproteins.

Degree: PhD, Biochemistry, 2018, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/101797

► Respiring organisms derive energy mainly from electron transfer reactions that are coupled to the translocation of ions across the cell membrane. This process is performed… (more)

▼ Respiring organisms derive energy mainly from electron transfer reactions that are coupled to the translocation of ions across the cell membrane. This process is performed by a group of membrane-localized protein complexes that hold different cofactors with redox properties, such as flavins, hemes, and other iron-containing centers. These redox complexes constitute the electron transport or respiratory chain. This thesis will cover the study of three different flavin-containing proteins related to the electron transport chain: • The type 2 NADH dehydrogenase (NDH-2) from Streptococcus agalactiae • The sulfide:quinone oxidoreductase (SQR) from the archaeon Caldivirga maquilingensis • The NDH-2 from Thermus thermophilus, now re-classified as a coenzyme A disulfide reductase (CoADR) NDH-2 catalyzes the same reaction (NADH:quinone oxidoreductase) as complex I, however it is unable to translocate protons across the membrane. Absent in mammalian mitochondria and the main or only respiratory NADH dehydrogenase present in certain pathogens, it has recently gained interest as a putative drug target. S. agalactiae is the major cause of meningitis and sepsis in a newborn’s first week of life in the United States. This organism encodes an NDH-2 as its only NADH dehydrogenase, and respiration has been shown to be important for virulence in an animal model. Here, NDH-2 was found to be the sole point of entry for electrons to the S. agalactiae respiratory chain. Additionally, in a mouse model of infection, mutant strains lacking NDH-2 showed significant attenuation for organ colonization. The protein was expressed, purified, biochemically characterized and used for in vitro screening of inhibitors. Several compounds were found to block activity of the protein and one even inhibited respiration in whole cells. SQRs (H2S + Q → S0 + QH2) are ubiquitous enzymes that can provide electrons to respiratory or photosynthetic electron transfer chains, besides having roles in sulfide detoxification and homeostasis. C. maquilingensis is a hyperthermophilic archaeon encoding a type III SQR, which lacks a cysteine residue involved in flavin binding in other SQR classes. This protein was expressed, purified and biochemically characterized, showing sulfide oxidation in the presence of quinone. The mode of membrane binding of CmSQR was studied by constructing truncated versions of the enzyme, lacking one or both amphipathic C-terminal helices. These variants were expressed as inactive soluble enzymes and lack of activity was attributed to the mutation of a single leucine residue, presumably involved in quinone interaction. Further mutations were made based on a homology model for CmSQR and crystal structures available for other SQR types, to characterize the quinone and flavin binding sites. Lastly, the oligomeric state of CmSQR was studied and the protein determined to be a dimer by different methods, including gel filtration, native gel and crosslinking. T. thermophilus aerobic NDH-2 exhibits very low activity (1 electron/sec) for NADH… Advisors/Committee Members: Gennis, Robert B. (advisor), Gennis, Robert B. (Committee Chair), Imlay, James A. (committee member), Chen, Lin-Feng (committee member), Oldfield, Eric (committee member).

Subjects/Keywords: flavoprotein; electron transport chain; nadh dehydrogenase; sulfide quinone reductase; coenzyme A disulfide reductase; Streptococcus agalactiae; Caldivirga maquilingensis; Thermus thermophilus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lencina, A. M. (2018). Biochemical characterization of respiratory chain flavoproteins. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/101797

Chicago Manual of Style (16^th Edition):

Lencina, Andrea Mariana. “Biochemical characterization of respiratory chain flavoproteins.” 2018. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/101797.

MLA Handbook (7^th Edition):

Lencina, Andrea Mariana. “Biochemical characterization of respiratory chain flavoproteins.” 2018. Web. 14 Apr 2021.

Vancouver:

Lencina AM. Biochemical characterization of respiratory chain flavoproteins. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/101797.

Council of Science Editors:

Lencina AM. Biochemical characterization of respiratory chain flavoproteins. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/101797

York University

12. Green, Alexander Edward. AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease.

Degree: MSc -MS, Kinesiology & Health Science, 2014, York University

URL: http://hdl.handle.net/10315/27571

► There are multiple copies of mtDNA per cell and each mtDNA molecule contains the information to encode 13 electron transport chain (ETC) proteins. When mtDNA… (more)

Subjects/Keywords: Physiology; Cellular biology; Kinesiology; mtDNA depletion syndrome; Mitochondria; mtDNA; AICAR; AMPK; Exercise; Mitochondrial disease; Oxidative phosphorylation; Electron transport chain; ETC

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Green, A. E. (2014). AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease. (Masters Thesis). York University. Retrieved from http://hdl.handle.net/10315/27571

Chicago Manual of Style (16^th Edition):

Green, Alexander Edward. “AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease.” 2014. Masters Thesis, York University. Accessed April 14, 2021. http://hdl.handle.net/10315/27571.

MLA Handbook (7^th Edition):

Green, Alexander Edward. “AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease.” 2014. Web. 14 Apr 2021.

Vancouver:

Green AE. AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease. [Internet] [Masters thesis]. York University; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10315/27571.

Council of Science Editors:

Green AE. AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease. [Masters Thesis]. York University; 2014. Available from: http://hdl.handle.net/10315/27571

University of Cambridge

13. Martinez Lyons, Anabel. The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes.

Degree: PhD, 2019, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/307269

► Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders typically associated with abnormal oxidative phosphorylation (OXPHOS). In recent years, next generation sequencing technologies… (more)

▼ Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders typically associated with abnormal oxidative phosphorylation (OXPHOS). In recent years, next generation sequencing technologies have allowed for accurate genetic diagnoses of inherited mitochondrial diseases directly from patient DNA by facilitating the identification of potential candidate genetic defects in either nuclear or mitochondrial genomes. In such a manner, two compound heterozygous sequence variants in COA7, which encodes a putative cytochrome c oxidase (Complex IV, COX) assembly factor, and homozygous recessive sequence variants in TMCO6, which encodes an uncharacterised protein, were identified in patients presenting with classical clinical and biochemical hallmarks of mitochondrial disease. The aim of this work was to 1) assess the pathogenicity of the COA7 and TMCO6 mutant variants in causing mitochondrial disease, and 2) to investigate the association of the resulting proteins in the assembly pathways of complexes of the mitochondrial respiratory chain: Complex IV (CIV, COX) for COA7 and Complex I (CI) for TMCO6. Compound heterozygous mutant variants in COA7 (NM_023077.3:c.410A>G;c.287+1G>T) led to total disappearance of its gene product in patient skin fibroblasts, owing to two aberrant mRNA transcripts. Loss of COA7 steady-state level correlated with low abundance of certain COX subunits, intermediates, monomeric and supercomplex COX species, as well as isolated COX enzymatic deficiency. Stable expression of COA7WT in patient fibroblasts by lentivirus-mediated complementation rescued COX abundance, the quantities of its affected subunits, subassembly and supercomplex species, and its activity, to normal levels, confirming the pathogenicity of the compound heterozygous COA7 mutant variants. A combination of super-resolution microscopy and subcellular fractionation and protease digestion studies confirmed the intracellular localisation of COA7 to be the mitochondrial intermembrane space. Secondly, a novel homozygous recessive variant in TMCO6 (NM_018502.5: c.271C>T) was identified in a paediatric proband presenting with severe developmental delay, generalised hypotonia and progressive cerebral and cerebellar atrophy. Biochemical measurement of a skeletal muscle biopsy revealed CI enzymatic deficiency, and patient-derived skin fibroblasts showed destabilisation of CI-containing supercomplexes. TMCO6 was found to co-localise with the CI holocomplex by 2D-BNGE, and this result was further corroborated by immunoprecipitation experiments. Additionally, cellular models for TMCO6 gene silencing and overexpression were characterised, and an attempted generation of a knockout cellular model is described. Subcellular fractionation and protease treatment experiments determined TMCO6 to localise to the mitochondrial inner membrane. A Tmco6-knockout murine model was characterised, which exhibited several neurological, physiological and motor debilities, isolated CI deficiency in heart and skeletal muscle, and abnormal cardiac…

Subjects/Keywords: mitochondrial medicine; mitochondrial disease; mitochondrial genetics; mitochondrial disease genes; OXPHOS assembly factors; electron transport chain; electron transport chain assembly factors; Complex I assembly factor; Complex IV assembly factors; COA7; TMCO6; whole exome sequencing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Martinez Lyons, A. (2019). The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/307269

Chicago Manual of Style (16^th Edition):

Martinez Lyons, Anabel. “The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes.” 2019. Doctoral Dissertation, University of Cambridge. Accessed April 14, 2021. https://www.repository.cam.ac.uk/handle/1810/307269.

MLA Handbook (7^th Edition):

Martinez Lyons, Anabel. “The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes.” 2019. Web. 14 Apr 2021.

Vancouver:

Martinez Lyons A. The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Apr 14]. Available from: https://www.repository.cam.ac.uk/handle/1810/307269.

Council of Science Editors:

Martinez Lyons A. The Molecular Anatomy of Mitochondrial Disease: Identification and Characterisation of Novel Nuclear-Encoded Mitochondrial Disease Genes. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/307269

University of Pretoria

14. [No author]. The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis .

Degree: 2007, University of Pretoria

URL: http://upetd.up.ac.za/thesis/available/etd-06182007-134849/

► The isolation and antimycobacterial activity of several naphthoquinones from Euclea natalensis were previously reported and initiated this study into the occurrence, chemistry and biological activity… (more)

▼ The isolation and antimycobacterial activity of several naphthoquinones from Euclea natalensis were previously reported and initiated this study into the occurrence, chemistry and biological activity of this class of compounds. The structure activity relationship of the isolated naphthoquinones, and commercially available derivatives were also studied. Several plant species were investigated to establish a possible link between their traditional use for chest related symptoms (including tuberculosis infection) and the occurrence of 7-methyljuglone in these plants. The plants were extracted and tested qualitatively with the use of three analytical tools for the presence of 7-methyljuglone or related naphthoquinones. Due to its commercial unavailability, the chemical synthesis of two of these naphthoquinones, 7-methyljuglone and diospyrin, was attempted with varying degrees of success. The Friedel-Crafts acylation method was used to synthesise 7-methyljuglone from m-cresol and maleic anhydride as starting material. The optimisation of the synthesis was also investigated. Through a two-step pathway of epoxidation and steam distillation, diospyrin was successfully synthesised albeit in small quantities. During the attempts to synthesise diospyrin, two other related compounds were also synthesised. These compounds, neodiospyrin and mamegakinone, are structural isomers of diospyrin. The stability of some of the naphthoquinones was tested in various carriers in an attempt to explain the influence this will have on the obtained antituberculosis and toxicity data. The BACTEC vial solution, which is widely used to determine potency against Mycobacterium tuberculosis, was analysed with HPLC to determine the stability of these compounds in it. In addition the stability in organic solvents especially DMSO, was also tested as this is the solvent of choice for hydrophobic compounds in almost all bioassays. The antituberculosis activity and/or toxicity of 7-methyljuglone was investigated with three bioassays, to broaden our knowledge on the mechanism of action of naphthoquinones. Vero cells were employed to determine the inhibitory concentration (IC50) of most of the naphthoquinones. Mice experiments were carried out to determine the toxicity of 7-methyljuglone and diospyrin in vivo. In addition the lead compound, 7-methyljuglone, was tested on Musca domestica (house fly) to establish its toxicity on this organism. In order to find the pharmacophore of this class of compounds, a preliminary structure-activity relationship was conducted. During this study the active site in the compounds which confers potency and toxicity was partly established. The mode of action of some of the naphthoquinones was investigated and it was established that the compounds might interfere with the mycobacterial electron transport chain. A fluorinated 7-methyljuglone stops the production of menaquinone which transports electrons from the NADH dehydrogenase complex to the cytochrome bc complex and effectively kills the mycobacterium. Advisors/Committee Members: Prof J J M Meyer (advisor).

Subjects/Keywords: Structure-activity relationship; Diospyrin; Electron transport chain; 7-methyljuglone; Mycobacterium tuberculosis; UCTD

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APA (6^th Edition):

author], [. (2007). The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis . (Doctoral Dissertation). University of Pretoria. Retrieved from http://upetd.up.ac.za/thesis/available/etd-06182007-134849/

Chicago Manual of Style (16^th Edition):

author], [No. “The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis .” 2007. Doctoral Dissertation, University of Pretoria. Accessed April 14, 2021. http://upetd.up.ac.za/thesis/available/etd-06182007-134849/.

MLA Handbook (7^th Edition):

author], [No. “The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis .” 2007. Web. 14 Apr 2021.

Vancouver:

author] [. The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis . [Internet] [Doctoral dissertation]. University of Pretoria; 2007. [cited 2021 Apr 14]. Available from: http://upetd.up.ac.za/thesis/available/etd-06182007-134849/.

Council of Science Editors:

author] [. The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis . [Doctoral Dissertation]. University of Pretoria; 2007. Available from: http://upetd.up.ac.za/thesis/available/etd-06182007-134849/

Stellenbosch University

15. Swart, Liezel Maria. The biochemical study of the R- and S-enantiomers of 2-(4-acetoxyphenyl)-2-chloro-Nmethylethylammonium chloride (Compound A).

Degree: MSc, Biochemistry, 2017, Stellenbosch University

URL: http://hdl.handle.net/10019.1/101101

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ENGLISH ABSTRACT: The study describes: . The synthesis of a racemic mixture of Compound A (2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium chloride), a synthetic analogue of the active compound isolated… (more)

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ENGLISH ABSTRACT: The study describes: . The synthesis of a racemic mixture of Compound A (2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium chloride), a synthetic analogue of the active compound isolated from the African shrub, Salsola tuberculataformis Botschantzev. . The development of a strategy to separate the R- and S-enantiomers of Compound A. . The isolation and purification of a highly purified substrate-free cytochrome P450 11β-hydroxylase (CYP11B1) from ovine adrenals. . The isolation of a partially purified mixture of the mitochondrial electron transport chain, adrenodoxin reductase and adrenodoxin from ovine adrenals. . The investigation into the mechanism of action of the R- and S-enantiomers of Compound A on the spectroscopic properties of substrate-free CYP11B1. . The investigation into the influence of the R- and S-enantiomers of Compound A on the mitochondrial electron transport chain by using cytochrome c as an electron acceptor.

AFRIKAANSE OPSOMMNG: Hierdie studie beskryf: . Die sintese van ‘n rasemiese mengsel van Verbinding A (2-(4-asetoksifeniel)-2-chloro-N-metielammoniumchloried), ‘n sintetiese analoog van die aktiewe molecule wat in die Suider-Afrikaanse plant, Salsola tuberculataformis Botschantzev. . Die ontwikkeling van 'n strategie om van die R- en S-enantiomere van Verbinding A te skei. . Die isolering en suiwering van ‘n hoogs gesuiwerde, substraat-vrye sitochroom P450 11β-hidroksilase (CYP11B1) uit skaap-byniere. . Die isolering van ‘n gedeeltelike gesuiwerde mengsel van die mitokondriale elektrontransportketting, adrenodoksienreduktase en adrenodoksien uit skaapbyniere. . ‘n Ondersoek na die meganisme van werking van die R- en S-enantiomere van Verbinding A op die spektroskopiese eienskappe van ‘n gesuiwerde substraat-vrye CYP11B1. . ‘n Ondersoek na die invloed van die R- en S-enantiomere van Verbinding A op die mitokondriale elektrontransportketting met behulp van sitochroom c as 'n elektronakseptor.

Advisors/Committee Members: Swart, Pieter, Swart, Amanda C., Stellenbosch University. Faculty of Science. Dept. of Biochemistry..

Subjects/Keywords: Salsola tuberculata – Namibia; Salsola tuberculata – Contraceptive properties; Adrenal steriodogenesis and cytochrome enzymes; Mitrochondrial electron transport chain isolation; Karakul ewes – Gestation; Karakul sheep – Abnormalities; UCTD

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APA (6^th Edition):

Swart, L. M. (2017). The biochemical study of the R- and S-enantiomers of 2-(4-acetoxyphenyl)-2-chloro-Nmethylethylammonium chloride (Compound A). (Masters Thesis). Stellenbosch University. Retrieved from http://hdl.handle.net/10019.1/101101

Chicago Manual of Style (16^th Edition):

Swart, Liezel Maria. “The biochemical study of the R- and S-enantiomers of 2-(4-acetoxyphenyl)-2-chloro-Nmethylethylammonium chloride (Compound A).” 2017. Masters Thesis, Stellenbosch University. Accessed April 14, 2021. http://hdl.handle.net/10019.1/101101.

MLA Handbook (7^th Edition):

Swart, Liezel Maria. “The biochemical study of the R- and S-enantiomers of 2-(4-acetoxyphenyl)-2-chloro-Nmethylethylammonium chloride (Compound A).” 2017. Web. 14 Apr 2021.

Vancouver:

Swart LM. The biochemical study of the R- and S-enantiomers of 2-(4-acetoxyphenyl)-2-chloro-Nmethylethylammonium chloride (Compound A). [Internet] [Masters thesis]. Stellenbosch University; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10019.1/101101.

Council of Science Editors:

Swart LM. The biochemical study of the R- and S-enantiomers of 2-(4-acetoxyphenyl)-2-chloro-Nmethylethylammonium chloride (Compound A). [Masters Thesis]. Stellenbosch University; 2017. Available from: http://hdl.handle.net/10019.1/101101

University of Pretoria

16. Van der Kooy, Frank. The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis.

Degree: Plant Science, 2007, University of Pretoria

URL: http://hdl.handle.net/2263/25601

► The isolation and antimycobacterial activity of several naphthoquinones from Euclea natalensis were previously reported and initiated this study into the occurrence, chemistry and biological activity… (more)

▼ The isolation and antimycobacterial activity of several naphthoquinones from Euclea natalensis were previously reported and initiated this study into the occurrence, chemistry and biological activity of this class of compounds. The structure activity relationship of the isolated naphthoquinones, and commercially available derivatives were also studied. Several plant species were investigated to establish a possible link between their traditional use for chest related symptoms (including tuberculosis infection) and the occurrence of 7-methyljuglone in these plants. The plants were extracted and tested qualitatively with the use of three analytical tools for the presence of 7-methyljuglone or related naphthoquinones. Due to its commercial unavailability, the chemical synthesis of two of these naphthoquinones, 7-methyljuglone and diospyrin, was attempted with varying degrees of success. The Friedel-Crafts acylation method was used to synthesise 7-methyljuglone from m-cresol and maleic anhydride as starting material. The optimisation of the synthesis was also investigated. Through a two-step pathway of epoxidation and steam distillation, diospyrin was successfully synthesised albeit in small quantities. During the attempts to synthesise diospyrin, two other related compounds were also synthesised. These compounds, neodiospyrin and mamegakinone, are structural isomers of diospyrin. The stability of some of the naphthoquinones was tested in various carriers in an attempt to explain the influence this will have on the obtained antituberculosis and toxicity data. The BACTEC vial solution, which is widely used to determine potency against Mycobacterium tuberculosis, was analysed with HPLC to determine the stability of these compounds in it. In addition the stability in organic solvents especially DMSO, was also tested as this is the solvent of choice for hydrophobic compounds in almost all bioassays. The antituberculosis activity and/or toxicity of 7-methyljuglone was investigated with three bioassays, to broaden our knowledge on the mechanism of action of naphthoquinones. Vero cells were employed to determine the inhibitory concentration (IC50) of most of the naphthoquinones. Mice experiments were carried out to determine the toxicity of 7-methyljuglone and diospyrin in vivo. In addition the lead compound, 7-methyljuglone, was tested on Musca domestica (house fly) to establish its toxicity on this organism. In order to find the pharmacophore of this class of compounds, a preliminary structure-activity relationship was conducted. During this study the active site in the compounds which confers potency and toxicity was partly established. The mode of action of some of the naphthoquinones was investigated and it was established that the compounds might interfere with the mycobacterial electron transport chain. A fluorinated 7-methyljuglone stops the production of menaquinone which transports electrons from the NADH dehydrogenase complex to the cytochrome bc complex and effectively kills the mycobacterium. Advisors/Committee Members: Prof J J M Meyer (advisor).

Subjects/Keywords: Structure-activity relationship; Diospyrin; Electron transport chain; 7-methyljuglone; Mycobacterium tuberculosis; UCTD

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APA (6^th Edition):

Van der Kooy, F. (2007). The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis. (Doctoral Dissertation). University of Pretoria. Retrieved from http://hdl.handle.net/2263/25601

Chicago Manual of Style (16^th Edition):

Van der Kooy, Frank. “The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis.” 2007. Doctoral Dissertation, University of Pretoria. Accessed April 14, 2021. http://hdl.handle.net/2263/25601.

MLA Handbook (7^th Edition):

Van der Kooy, Frank. “The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis.” 2007. Web. 14 Apr 2021.

Vancouver:

Van der Kooy F. The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis. [Internet] [Doctoral dissertation]. University of Pretoria; 2007. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2263/25601.

Council of Science Editors:

Van der Kooy F. The medicinal and chemical aspects of naphthoquinones isolated from Euclea natalensis A. DC. on Mycobacterium tuberculosis. [Doctoral Dissertation]. University of Pretoria; 2007. Available from: http://hdl.handle.net/2263/25601

Arizona State University

17. Dey, Sriloy. Synthesis and Evaluation of Multifunctional Radical Quenchers for the Protection of Mitochondrial Function.

Degree: Chemistry, 2015, Arizona State University

URL: http://repository.asu.edu/items/34800

Subjects/Keywords: Chemistry; Organic chemistry; Electron transport chain; Mitochondria; Mitochondrial drug; MRQ; Organic chemistry; Synthesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dey, S. (2015). Synthesis and Evaluation of Multifunctional Radical Quenchers for the Protection of Mitochondrial Function. (Doctoral Dissertation). Arizona State University. Retrieved from http://repository.asu.edu/items/34800

Chicago Manual of Style (16^th Edition):

Dey, Sriloy. “Synthesis and Evaluation of Multifunctional Radical Quenchers for the Protection of Mitochondrial Function.” 2015. Doctoral Dissertation, Arizona State University. Accessed April 14, 2021. http://repository.asu.edu/items/34800.

MLA Handbook (7^th Edition):

Dey, Sriloy. “Synthesis and Evaluation of Multifunctional Radical Quenchers for the Protection of Mitochondrial Function.” 2015. Web. 14 Apr 2021.

Vancouver:

Dey S. Synthesis and Evaluation of Multifunctional Radical Quenchers for the Protection of Mitochondrial Function. [Internet] [Doctoral dissertation]. Arizona State University; 2015. [cited 2021 Apr 14]. Available from: http://repository.asu.edu/items/34800.

Council of Science Editors:

Dey S. Synthesis and Evaluation of Multifunctional Radical Quenchers for the Protection of Mitochondrial Function. [Doctoral Dissertation]. Arizona State University; 2015. Available from: http://repository.asu.edu/items/34800

University of Melbourne

18. Rathnapala, Gallallalage Upeksha Lakmini. Defining the roles of essential genes in the malaria parasite life cycle.

Degree: 2017, University of Melbourne

URL: http://hdl.handle.net/11343/207955

► The combination of drug resistance, lack of an effective vaccine and ongoing conflict and poverty mean that malaria remains a major global health crisis. Understanding… (more)

▼ The combination of drug resistance, lack of an effective vaccine and ongoing conflict and poverty mean that malaria remains a major global health crisis. Understanding metabolic pathways at all parasite life stages is important in prioritising and targeting novel anti-parasitic compounds. To overcome limitations of existing genetic tools to investigate all the parasite life stages, new approaches are vital. This project aimed to develop a novel genetic approach using post meiotic segregation to separate genes and bridge parasites through crucial life stages. The unusual heme synthesis pathway of the rodent malaria parasite, Plasmodium berghei, requires eight enzymes distributed across the mitochondrion, apicoplast and cytoplasm. Deletion of the ferrochelatase (FC) gene, the final enzyme in the pathway, confirms that heme synthesis is not essential in the red blood cell stages of the life cycle but is required to complete oocyst development in mosquitoes. The lethality of FC deletions in the mosquito stage makes it difficult to study the impact of these mutations in the subsequent liver stage. To overcome this, I combined locus-specific fluorophore expression with a genetic complementation approach to generate viable, heterozygous oocysts able to produce a mix of FC expressing and FC deficient sporozoites. In the liver stage, FC deficient parasites can be distinguished by fluorescence and phenotyped. Parasites lacking FC exhibited a severe growth defect from early to mid-stages of liver development in-vitro and could not infect naïve mice, confirming liver stage arrest. These results validate the heme pathway as a potential target for prophylactic drugs targeting liver stage parasites. Energy metabolism in malaria parasites varies remarkably over the parasite life cycle. Parasites depend solely on anaerobic glycolysis at blood stage but need Krebs cycle, the electron transport chain, and mitochondrial ATP synthase during mosquito stage development. Again, reverse genetic approaches to study the hepatic stage of Plasmodium have been thwarted because parasites with defects in energy pathways are unable to complete the mosquito stage. I used the genetic complementation approach established to study heme biosynthesis to bridge parasites lacking the β subunit of mitochondrial ATP synthase through mosquito stage and studied their development in the liver stage. ATPase knockouts were indistinguishable from wildtype in in-vitro liver stage assays of size, nuclear content, and merosome production. Robust progression to blood stage confirmed the dispensability of mitochondrial ATP synthesis in liver stages. I extended this approach to explore the essentiality of upstream mitochondrial electron transport and Krebs cycle during the liver stage. I speculate that energy metabolism in the liver stage resembles that in the blood stage, relying predominantly on glycolysis for ATP production. There are numerous genetic tools to manipulate the blood stage malaria parasite genome in general, but existing genetic tools to…

Subjects/Keywords: malaria; Plasmodium berghei; heme; ferrochelatase; ATP synthase; krebs cycle; electron transport chain; isoprenoid precursor biosynthesis pathway; complementation, exo- erythrocytic; liver; fluorescence; sporozoite; oocyst

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rathnapala, G. U. L. (2017). Defining the roles of essential genes in the malaria parasite life cycle. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/207955

Chicago Manual of Style (16^th Edition):

Rathnapala, Gallallalage Upeksha Lakmini. “Defining the roles of essential genes in the malaria parasite life cycle.” 2017. Doctoral Dissertation, University of Melbourne. Accessed April 14, 2021. http://hdl.handle.net/11343/207955.

MLA Handbook (7^th Edition):

Rathnapala, Gallallalage Upeksha Lakmini. “Defining the roles of essential genes in the malaria parasite life cycle.” 2017. Web. 14 Apr 2021.

Vancouver:

Rathnapala GUL. Defining the roles of essential genes in the malaria parasite life cycle. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/11343/207955.

Council of Science Editors:

Rathnapala GUL. Defining the roles of essential genes in the malaria parasite life cycle. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/207955

University of Melbourne

19. Mot, Alexandra Ioana. Mitochondria and energy metabolism in cell culture models of motor neuron disease.

Degree: 2016, University of Melbourne

URL: http://hdl.handle.net/11343/123727

► Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the selective loss of motor neurons. Although a relatively small proportion of all ALS… (more)

▼ Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the selective loss of motor neurons. Although a relatively small proportion of all ALS cases are caused by familial mutations in proteins such as superoxide dismutase 1 (SOD1) and transactive response DNA binding protein 43 (TDP43), shared clinical and pathological features across sporadic and familial cases of ALS suggest that both may share a common underlying mechanism. The reasons why motor neurons are primarily affected in ALS, particularly in those cases caused by a ubiquitously expressed mutation, remain unknown. Given the disproportionately high energy demand of motor neurons when compared to other cell types, and the wealth of evidence demonstrating the role of impaired energy metabolism in both sporadic and familial ALS, it is possible that the selectivity of motor neuron death in ALS involves impaired energy metabolism. To investigate this possibility, a better understanding of the mechanisms leading to impaired energy metabolism in ALS is needed, and this is dependent upon the availability of valid models. Although neurons in the body are largely dependent on mitochondrial oxidative phosphorylation (OXPHOS) to meet the bulk of their energy demands, most cultured cells generate the bulk of their energy via glycolysis. Substituting medium glucose with galactose is one way of increasing OXPHOS in cultured cells, however galactose is not normally present in the central nervous system (CNS). Commonly used cell culture conditions, therefore, limit the ability to extrapolate results obtained under such conditions to in vivo neurons. As such, the hypothesis of this thesis was that increasing reliance on mitochondrial OXPHOS in cultured cells in a way that more closely replicates the in vivo energy metabolism of neurons will expose energy metabolism deficits due to ALS-causing mutations. To establish a cell culture model in which cells have an increased reliance on mitochondrial OXPHOS in a way that more closely replicates the in vivo energy metabolism of neurons (Aim 1), primary cortical neurons were initially utilised for this study. However, due to the slow consumption of extracellular glucose cultured neurons could not be easily driven towards dependence on extracellular lactate as the primary fuel of mitochondrial OXPHOS. In subsequent experiments an alternative cell type, primary mouse embryonic fibroblasts (pMEFs), were grown in medium containing 3.5 mM glucose and two phases of growth were identified: the initial glucose-consuming (i.e. glycolytic) phase followed by the lactate-consuming (i.e. OXPHOS) phase. The lactate-consuming phase was characterised by increased Mito-Tracker Deep Red staining intensity, increased expression of nuclear-encoded mitochondrial proteins, and increased sensitivity to the OXPHOS inhibitor rotenone. Thus, by inducing cell autonomous depletion of glucose from the culture medium cells were forced cells to utilise extracellular lactate via mitochondrial OXPHOS to supply…

Subjects/Keywords: Amyotrophic lateral sclerosis (ALS); superoxide dismutase 1 (SOD1); transactive response DNA binding protein 43 (TDP43); cell culture; mitochondria; lactate; oxidative phosphorylation (OXPHOS); electron transport chain (ETC)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mot, A. I. (2016). Mitochondria and energy metabolism in cell culture models of motor neuron disease. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/123727

Chicago Manual of Style (16^th Edition):

Mot, Alexandra Ioana. “Mitochondria and energy metabolism in cell culture models of motor neuron disease.” 2016. Doctoral Dissertation, University of Melbourne. Accessed April 14, 2021. http://hdl.handle.net/11343/123727.

MLA Handbook (7^th Edition):

Mot, Alexandra Ioana. “Mitochondria and energy metabolism in cell culture models of motor neuron disease.” 2016. Web. 14 Apr 2021.

Vancouver:

Mot AI. Mitochondria and energy metabolism in cell culture models of motor neuron disease. [Internet] [Doctoral dissertation]. University of Melbourne; 2016. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/11343/123727.

Council of Science Editors:

Mot AI. Mitochondria and energy metabolism in cell culture models of motor neuron disease. [Doctoral Dissertation]. University of Melbourne; 2016. Available from: http://hdl.handle.net/11343/123727

University of Georgia

20. Altharawi, Ali Ibrahim. Design and synthesis of NADH mimics that target mitochondrial electron transport of plasmodium parasite.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/28962

► Malaria, particularly that caused by Plasmodium falciparum, remains one of the most deadly infectious diseases worldwide. Unfortunately, multi–drug resistance (MDR) to currently used antimalarials has… (more)

Subjects/Keywords: Plasmodium falciparum; multi-drug resistance (MDR); mitochondrial electron transport chain (mtETC); Triphenylphosphonium (TPP); 4(1H)-pyridinone; W2 chloroquine-resistant Plasmodium falciparum; IC50s; NADH dehydrogenase (Complex I); food vacuole (FV)

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APA (6^th Edition):

Altharawi, A. I. (2014). Design and synthesis of NADH mimics that target mitochondrial electron transport of plasmodium parasite. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/28962

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Altharawi, Ali Ibrahim. “Design and synthesis of NADH mimics that target mitochondrial electron transport of plasmodium parasite.” 2014. Thesis, University of Georgia. Accessed April 14, 2021. http://hdl.handle.net/10724/28962.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Altharawi, Ali Ibrahim. “Design and synthesis of NADH mimics that target mitochondrial electron transport of plasmodium parasite.” 2014. Web. 14 Apr 2021.

Vancouver:

Altharawi AI. Design and synthesis of NADH mimics that target mitochondrial electron transport of plasmodium parasite. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/10724/28962.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Altharawi AI. Design and synthesis of NADH mimics that target mitochondrial electron transport of plasmodium parasite. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/28962

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

The Ohio State University

21. Rauckhorst, Adam J. Towards the Regulation and Physiological Role of the Mitochondrial Calcium- Independent Phospholipase A₂.

Degree: PhD, Integrated Biomedical Science Graduate Program, 2014, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1416930755

► Mitochondria are organelles found within most eukaryotic cell types that are primarily responsible for bulk ATP production that is required for cell survival. Additionally,… (more)

▼ Mitochondria are organelles found within most eukaryotic cell types that are primarily responsible for bulk ATP production that is required for cell survival. Additionally, mitochondria sequester pro-apoptotic factors and release them upon initiation of the apoptotic process. Based on these two fundamental roles, it is easy to understand how mitochondria are essential in determining the health of the cell. In fact, damage to mitochondria has been shown to be the principal insult during many forms of ischemia/reperfusion injury, such as a heart attack or stroke. During an ischemic event, an area of tissue is prevented from receiving oxygen and substrate rich blood by the blockage of an artery. The area of tissue becomes hypoxic and mitochondria are unable to perform the processes required to generate ATP for the cell. Conditions which accompany ischemia can cause the opening of an indiscriminate mitochondrial inner membrane pore and allow the equilibration of solutes less than 1500 Daltons during a process known as the mitochondrial permeability transition [MPT]. After the mitochondria have undergone the MPT cells will progress through apoptosis or necrosis leading to an area infarct observed after heart attack or stroke. Currently, the pore that opens to cause the MPT is not known, however previous work by our group and others have shown that the activity of a mitochondrial calcium- independent phospholipase A₂ [iPLA₂] accompanies MPT and sensitizes the pore opening. We first identified the iPLA₂ activity in isolated mitochondria upon uncoupling of the electron transport chain from ATP synthesis, opening of the pore responsible for the MPT, and by forming an artificial pore in the mitochondrial membrane using alamethicin. Additionally, we showed that there was no discernable iPLA₂ activity in energized mitochondria. With this in mind, we hypothesized that the iPLA₂ was specifically regulated by the loss of membrane potential that accompanied all of the previously identified activators. Utilizing isolated mitochondria, we have developed a model system in which we can selectively modulate the generation of membrane potential via the inhibition of specific components of the electron transport chain. Using this system we can assess the ability of the iPLA₂ to become active upon loss of membrane potential. We have also used this system to examine the role of the iPLA₂ in other possible physiological processes. Here we show that the mitochondrial iPLA₂ is primarily regulated by small decreases in membrane potential and is reversible upon reenergization. Additionally, we propose a new potential physiological function for mitochondrial stress induced iPLA₂ activity. As mentioned above, iPLA₂ activity sensitizes the pore responsible for the MPT to opening. Because iPLA₂ activity occurs upstream of the MPT, we propose that the iPLA₂ could serve as a pharmacological target to… Advisors/Committee Members: Pfeiffer, Douglas (Advisor).

Subjects/Keywords: Biochemistry; Biomedical Research; Mitochondria; bioenergetics; electron transport chain; phospholipase A2; Calcium-independent phospholipase A2; mitochondrial dynamics; mitophagy; mitochondrial permeability transition; mitochondrial permeability transition pore

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rauckhorst, A. J. (2014). Towards the Regulation and Physiological Role of the Mitochondrial Calcium- Independent Phospholipase A₂. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1416930755

Chicago Manual of Style (16^th Edition):

Rauckhorst, Adam J. “Towards the Regulation and Physiological Role of the Mitochondrial Calcium- Independent Phospholipase A₂.” 2014. Doctoral Dissertation, The Ohio State University. Accessed April 14, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1416930755.

MLA Handbook (7^th Edition):

Rauckhorst, Adam J. “Towards the Regulation and Physiological Role of the Mitochondrial Calcium- Independent Phospholipase A₂.” 2014. Web. 14 Apr 2021.

Vancouver:

Rauckhorst AJ. Towards the Regulation and Physiological Role of the Mitochondrial Calcium- Independent Phospholipase A₂. [Internet] [Doctoral dissertation]. The Ohio State University; 2014. [cited 2021 Apr 14]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1416930755.

Council of Science Editors:

Rauckhorst AJ. Towards the Regulation and Physiological Role of the Mitochondrial Calcium- Independent Phospholipase A₂. [Doctoral Dissertation]. The Ohio State University; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1416930755

22. Lin, Paul P. Superoxide Dismutase 2 Overexpression Attenuates Effects of Ischemia Reperfusion-Induced Mitochondrial Dysfunction.

Degree: MS, Integrated Pharmaceutical Medicine, 2017, NEOMED Integrated Pharmaceutical Medicine

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1506511457775683

► Myocardial ischemia reperfusion (IR) injury has been shown to cause mitochondrial dysfunction. The electron transport chain (ETC) is a major source of superoxide and other… (more)

Subjects/Keywords: Biology; Superoxide; SOD2; MnSOD; Heart; Heart Mitochondria; Mitochondria; Electron transport chain; Antioxidant; Ischemia Reperfusion; IR; Krebs Cycle; Catalase; Glutathione Peroxidas; Oxidative Stress

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lin, P. P. (2017). Superoxide Dismutase 2 Overexpression Attenuates Effects of Ischemia Reperfusion-Induced Mitochondrial Dysfunction. (Masters Thesis). NEOMED Integrated Pharmaceutical Medicine. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1506511457775683

Chicago Manual of Style (16^th Edition):

Lin, Paul P. “Superoxide Dismutase 2 Overexpression Attenuates Effects of Ischemia Reperfusion-Induced Mitochondrial Dysfunction.” 2017. Masters Thesis, NEOMED Integrated Pharmaceutical Medicine. Accessed April 14, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1506511457775683.

MLA Handbook (7^th Edition):

Lin, Paul P. “Superoxide Dismutase 2 Overexpression Attenuates Effects of Ischemia Reperfusion-Induced Mitochondrial Dysfunction.” 2017. Web. 14 Apr 2021.

Vancouver:

Lin PP. Superoxide Dismutase 2 Overexpression Attenuates Effects of Ischemia Reperfusion-Induced Mitochondrial Dysfunction. [Internet] [Masters thesis]. NEOMED Integrated Pharmaceutical Medicine; 2017. [cited 2021 Apr 14]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1506511457775683.

Council of Science Editors:

Lin PP. Superoxide Dismutase 2 Overexpression Attenuates Effects of Ischemia Reperfusion-Induced Mitochondrial Dysfunction. [Masters Thesis]. NEOMED Integrated Pharmaceutical Medicine; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ne2mh1506511457775683

23. Felippe Henrique Zuccolotto dos Reis. Estudo da cadeia transportadora de elétrons na intolerância ao exercício decorrente de deleções múltiplas no DNA mitocondrial.

Degree: 2019, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/17/17140/tde-18122019-150201/

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Intolerância ao exercício (IE) é a incapacidade de desempenhar atividade física normalmente, ocorrendo sintomas como mialgia e fadiga precoce, mesmo em resposta a exercícios relativamente… (more)

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Intolerância ao exercício (IE) é a incapacidade de desempenhar atividade física normalmente, ocorrendo sintomas como mialgia e fadiga precoce, mesmo em resposta a exercícios relativamente leves. A importância deste trabalho está no fato de que a IE é um problema frequente na prática clínica, que resulta em marcante incapacidade física em decorrência da dificuldade no estabelecimento de sua etiologia, e consequentemente no adequado manejo dos sintomas. A elucidação das suas bases fisiopatológicas tem papel potencial no estabelecimento de uma abordagem terapêutica mais efetiva. Objetivamos avaliar a repercussão das deleções múltiplas no DNA mitocondrial (mtDNA) no funcionamento da cadeia transportadora de elétrons (CTE) em pacientes com IE. Selecionamos três grupos de pacientes: 13 pacientes com IE e deleções múltiplas no mtDNA formaram o grupo de IE; dois pacientes com encefalomiopatia mitocondrial, acidose láctica e episódios semelhantes a acidente vascular cerebral (MELAS) e mutação 3243A>G, e mais dois pacientes com oftalmoplegia externa progressiva (PEO) e deleção única no mtDNA constituíram o grupo de pacientes com doença mitocondrial (DM); sete pacientes que tiveram o diagnóstico de DM descartado e sem indícios de disfunção mitocondrial formaram o grupo controle. Os dados clínico-laboratoriais foram obtidos do prontuário médico. Os fragmentos das biópsias foram analisados por histopatologia, por ensaios enzimáticos via espectrofotômetro e fluorímetro, e pelo consumo de O2 da CTE via eletrodo de alta resolução. Os achados à biópsia muscular dos pacientes com IE e deleções múltiplas do mtDNA consistiram de anormalidades discretas e em geral inespecíficas, porém a maioria dos pacientes apresentou fibras com aumento subsarcolemal de mitocôndrias. Os ensaios enzimáticos demonstraram redução de 24% a 40% a atividade dos complexos da CTE. O consumo de O2 foi padronizado em homogeneizados de biópsias congeladas, utilizando o protocolo com adição sequencial do citocromo c, do NAD+,do malato e do acetil CoA como substratos, e da rotenona, do malonato e da antimicina A como inibidores, pois foi o que demonstrou maior reprodutibilidade. Os pacientes IE tiveram uma redução significativa no consumo de O2 da CTE quando comparado ao grupo controle. O consumo de O2 e as atividades enzimáticas de cada complexo da CTE estudados separadamente correlacionaram-se positivamente. Estes dados juntamente com o exame clínico-laboratorial confirmaram o efeito prejudicial das deleções múltiplas no mtDNA na função mitocondrial dos pacientes com IE.

Exercise intolerance (EI) is the inability to perform physical activity normally, occurring symptoms such as myalgia and early fatigue, even in response to relatively light exercise. The importance of this work is the fact that EI is a frequent problem in clinical practice, which results in marked physical incapacity due to the difficulty in establishing its etiology, and consequently in the appropriate management of symptoms. The elucidation of its pathophysiological bases has a…

Advisors/Committee Members: Claudia Ferreira da Rosa Sobreira, Wilson Marques Júnior.

Subjects/Keywords: Cadeia transportadora de elétrons; Consumo de O2; Doença mitocondrial; Intolerância ao exercício; Mitocôndria; Electron transport chain; Exercise intolerance; Mitochondria; Mitochondrial disease; O2 consumption

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Reis, F. H. Z. d. (2019). Estudo da cadeia transportadora de elétrons na intolerância ao exercício decorrente de deleções múltiplas no DNA mitocondrial. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/17/17140/tde-18122019-150201/

Chicago Manual of Style (16^th Edition):

Reis, Felippe Henrique Zuccolotto dos. “Estudo da cadeia transportadora de elétrons na intolerância ao exercício decorrente de deleções múltiplas no DNA mitocondrial.” 2019. Doctoral Dissertation, University of São Paulo. Accessed April 14, 2021. http://www.teses.usp.br/teses/disponiveis/17/17140/tde-18122019-150201/.

MLA Handbook (7^th Edition):

Reis, Felippe Henrique Zuccolotto dos. “Estudo da cadeia transportadora de elétrons na intolerância ao exercício decorrente de deleções múltiplas no DNA mitocondrial.” 2019. Web. 14 Apr 2021.

Vancouver:

Reis FHZd. Estudo da cadeia transportadora de elétrons na intolerância ao exercício decorrente de deleções múltiplas no DNA mitocondrial. [Internet] [Doctoral dissertation]. University of São Paulo; 2019. [cited 2021 Apr 14]. Available from: http://www.teses.usp.br/teses/disponiveis/17/17140/tde-18122019-150201/.

Council of Science Editors:

Reis FHZd. Estudo da cadeia transportadora de elétrons na intolerância ao exercício decorrente de deleções múltiplas no DNA mitocondrial. [Doctoral Dissertation]. University of São Paulo; 2019. Available from: http://www.teses.usp.br/teses/disponiveis/17/17140/tde-18122019-150201/

24. Mateus Prates Mori. Novo papel da proteína XPC na regulação dos complexos da cadeia de transporte de elétrons e desequilíbrio redox.

Degree: 2015, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/46/46131/tde-20072015-105008/

► Espécies reativas de oxigênio (EROs) são normalmente e continuamente geradas em mitocôndrias, majoritariamente na cadeia de transporte de elétrons (CTE). Harman (1956, 1972 e 1992)… (more)

▼ Espécies reativas de oxigênio (EROs) são normalmente e continuamente geradas em mitocôndrias, majoritariamente na cadeia de transporte de elétrons (CTE). Harman (1956, 1972 e 1992) teorizou que os radicais livres gerados nas mitocôndrias seriam a principal causa do envelhecimento. De fato, durante o envelhecimento é observado um desequilíbrio entre formação e remoção de EROs, que resulta em estresse redox. Essa condição favorece a formação de lesões oxidadas no DNA, acarretando em mutagênese ou morte celular. Diversos mecanismos moleculares cooperam para o reparo de DNA. Duas vias de reparo de DNA lidam com a maioria das lesões: o reparo por excisão de base (BER) e o reparo por excisão de nucleotídeos (NER). A via BER corrige pequenas modificações de bases que surgem de reações de desaminação, alquilação e oxidação. A via NER é mais versátil, reconhecendo lesões que distorcem a dupla hélice de DNA, como danos induzidos por luz UV e adutos volumos. Pacientes xeroderma pigmentoso (XP-A a XP-G) herdam mutações em um de sete genes que codificam proteínas envolvidas na via NER, ou em um gene que codifica uma polimerase translesão (XP-V). A doença é caracterizada por fotosensibilidade e incidência elevada de neoplasias cutâneas. A proteína XPC atua na etapa de reconhecimento da lesão de DNA na subvia de reparo global do genoma (GG-NER), e sua mutação dá origem aos sintomas clássicos de XP. Novas funções de XPC foram recentemente descritas: i) atuando como cofator na via BER auxiliando as DNA glicosilases OGG1, TDG e SMUG; ii) atuando como cofator transcricional de elementos responsivos a Oct4/Sox2, RXR e PPARα; e iii) na adaptação metabólica na transformação de queratinócitos. Então, propusemo-nos a investigar as relações entre XPC e a manutenção da integridade do DNA mitocondrial, a sensibilidade celular a estresse redox mitocondrial e possíveis alterações bioenergéticas e redox. Para tal, padronizamos um ensaio in vitro de cinética de incisão em DNA plasmidial a fim de investigarmos o possível papel de XPC no reparo de lesões oxidadas em mtDNA. Porém, nossos dados revelaram que XPC não se encontra em mitocôndrias. Apesar disso, células XP-C são mais sensíveis ao tratamento com azul de metileno (AM), antimicina A (AA) e rotenona (ROT), que geram estresse redox mitocondrial. A sensibilidade à AA foi completamente revertida em células corrigidas. Células XP-C apresentaram alterações quanto ao uso dos complexos mitocondriais, com diminuição da taxa de consumo de oxigênio (OCR) via complexo I e um aumento da OCR via complexo II, dependente da presença de XPC. Ademais, a linhagem XP-C apresentou um desequilíbrio redox mitocondrial com maior produção de EROs e menor atividade de GPx. O DNA mitocondrial de células XP-C apresentou níveis elevados de lesão e deleção, que no entanto não retornaram aos níveis encontrados em células selvagens na linhagem XP-C corrigida. Observamos uma acentuada diminuição da expressão de PPARGC1A, um importante regulador de biogênese mitocondrial. Contudo, não foi possível determinar o mecanismo… Advisors/Committee Members: Nadja Cristhina de Souza-Pinto, Mauricio da Silva Baptista, Roger Frigerio Castilho, Rodrigo da Silva Galhardo, Marisa Helena Gennari de Medeiros.

Subjects/Keywords: Complexos da cadeia de transporte de elétrons; Desequilíbrio redox; PPARGC1A; Regulação; Reparação do DNA; XPC; Electron transport chain complexes; PPARGC1A; Redox imbalance; Regulation; Repair of DNA; XPC

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mori, M. P. (2015). Novo papel da proteína XPC na regulação dos complexos da cadeia de transporte de elétrons e desequilíbrio redox. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/46/46131/tde-20072015-105008/

Chicago Manual of Style (16^th Edition):

Mori, Mateus Prates. “Novo papel da proteína XPC na regulação dos complexos da cadeia de transporte de elétrons e desequilíbrio redox.” 2015. Doctoral Dissertation, University of São Paulo. Accessed April 14, 2021. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-20072015-105008/.

MLA Handbook (7^th Edition):

Mori, Mateus Prates. “Novo papel da proteína XPC na regulação dos complexos da cadeia de transporte de elétrons e desequilíbrio redox.” 2015. Web. 14 Apr 2021.

Vancouver:

Mori MP. Novo papel da proteína XPC na regulação dos complexos da cadeia de transporte de elétrons e desequilíbrio redox. [Internet] [Doctoral dissertation]. University of São Paulo; 2015. [cited 2021 Apr 14]. Available from: http://www.teses.usp.br/teses/disponiveis/46/46131/tde-20072015-105008/.

Council of Science Editors:

Mori MP. Novo papel da proteína XPC na regulação dos complexos da cadeia de transporte de elétrons e desequilíbrio redox. [Doctoral Dissertation]. University of São Paulo; 2015. Available from: http://www.teses.usp.br/teses/disponiveis/46/46131/tde-20072015-105008/

Arizona State University

25. Waskasi, Morteza. Temperature and Polarizability Effects on Electron Transfer in Biology and Artificial Photosynthesis.

Degree: Chemistry, 2019, Arizona State University

URL: http://repository.asu.edu/items/54801

Subjects/Keywords: Molecular chemistry; Chemistry; Biochemistry; C60; Dielectric constant; Electron Transfer; Electron transport chain; Marcus Theory; Reorganization Energy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Waskasi, M. (2019). Temperature and Polarizability Effects on Electron Transfer in Biology and Artificial Photosynthesis. (Doctoral Dissertation). Arizona State University. Retrieved from http://repository.asu.edu/items/54801

Chicago Manual of Style (16^th Edition):

Waskasi, Morteza. “Temperature and Polarizability Effects on Electron Transfer in Biology and Artificial Photosynthesis.” 2019. Doctoral Dissertation, Arizona State University. Accessed April 14, 2021. http://repository.asu.edu/items/54801.

MLA Handbook (7^th Edition):

Waskasi, Morteza. “Temperature and Polarizability Effects on Electron Transfer in Biology and Artificial Photosynthesis.” 2019. Web. 14 Apr 2021.

Vancouver:

Waskasi M. Temperature and Polarizability Effects on Electron Transfer in Biology and Artificial Photosynthesis. [Internet] [Doctoral dissertation]. Arizona State University; 2019. [cited 2021 Apr 14]. Available from: http://repository.asu.edu/items/54801.

Council of Science Editors:

Waskasi M. Temperature and Polarizability Effects on Electron Transfer in Biology and Artificial Photosynthesis. [Doctoral Dissertation]. Arizona State University; 2019. Available from: http://repository.asu.edu/items/54801

Université Paris-Sud – Paris XI

26. Wu, Qian. Regulation of mitochondrial ATPase by its inhibitor protein IF1 in Saccharomyces cerevisiae : Régulation de l’ATP synthase mitochondriale par son inhibiteur endogène IF1 chez Saccharomyces cerevisiae.

Degree: Docteur es, Biochimie et biologie moléculaire, 2013, Université Paris-Sud – Paris XI

URL: http://www.theses.fr/2013PA11T097

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ATP synthase est une protéine essentielle associée à la membrane interne mitochondriale, qui synthétise l'ATP par couplage d’un transport de protons au travers de la… (more)

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ATP synthase est une protéine essentielle associée à la membrane interne mitochondriale, qui synthétise l'ATP par couplage d’un transport de protons au travers de la membrane, en dissipant un gradient électrochimique de protons créé par la chaîne respiratoire. Cette réaction assure l’alimentation en énergie des processus biologiques cellulaires. Si la membrane mitochondriale se dépolarise, la réaction inverse d’hydrolyse d’ATP est rapidement bloquée par un inhibiteur soluble naturel de l’ATPase mitochondriale, IF1. Cette régulation efficace et réversible évite le gaspillage de l’énergie par la cellule. Chez la levure, IF1 est une petite protéine de 63 amino-acides. Elle se fixe sur l'une des trois interfaces catalytiques de l’ATP synthase et inhibe l’hydrolyse d’ATP. Bien que les structures cristallographiques des complexes F1-ATPase inhibés par IF1 aient été résolus, l'étape initiale de reconnaissance et celle du verrouillage d’IF1 restent peu claires au niveau moléculaire.Pendant ma thèse, nous nous sommes intéressés au mécanisme d’inhibition de l’ATPase par IF1. Par des analyses des structures disponibles et des alignements de séquence, nous avons sélectionné de nombreux résidus localisés dans différentes régions des sous-unités α et β de l'ATP synthase de Saccharomyces cerevisiae et susceptibles de participer au processus de fixation d'IF1. En utilisant le mutagenèse dirigée combinée à des experiences cinétiques, nous avons étudié les effects des mutations sur l’inhibition de l’ATP synthase par IF1 chez Saccharomyces cerevisiae. Dans ce travail, nous avons identifié des résidus ou motifs des sous-unités α et β de l’ATP synthase impliqués dans les étapes de reconaissance et/ou verrouillage d’IF1, ce qui nous permet de compléter les études structurales et d'esquisser un mécanisme de fixation d'IF1.

ATP synthase is an essential protein complex located in the mitochondrial inner membrane, which synthesize ATP by coupling to a rotary proton transport across the membrane at the expense of the electrochemical proton gradient created by the electron transport chain. This reaction guarantees the supply of energy to biological processes in a cell. When mitochondria get deenergized, i.e. the protomotive force across the mitochondrial inner membrane collapses, the ATP synthase switches from ATP synthesis to hydrolysis. This hydrolytic activity is then immediately prevented by a natural soluble mitochondrial ATPase inhibitor, IF1. This efficient reversible inhibition system protects cells from wasting energy. In yeast, IF1 is a small protein consisting of 63 amino acids. It binds to one of the three (αβ) catalytic interfaces of ATP synthase and thereby blocks the rotary catalysis. Although the crystal structure of the dead-end IF1 inhibited F1-ATPase complex has been resolved, IF1 initial binding and locking to ATPase still remain unclear events at the molecular level.During my thesis, we have been interested in the dynamic mechanism of ATPase inhibition by IF1. By means of analyses of published structures and protein…

Advisors/Committee Members: Haraux, Francis (thesis director).

Subjects/Keywords: Mitochondrie; ATP synthase; Rotation; Force protomotrice; Chaîne de transport d'électrons; Inhibition d’IF1; Reconnaissance et verrouillage d’IF1; Mutagenèse; Cinétique; Kon; Koff; Kd; Mitochondria; ATP synthase; Rotation; Protomotive force; Electron transport chain; IF1 inhibition; IF1 recognition and locking; Mutagenesis; Kinetics; Kon; Koff; Kd

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wu, Q. (2013). Regulation of mitochondrial ATPase by its inhibitor protein IF1 in Saccharomyces cerevisiae : Régulation de l’ATP synthase mitochondriale par son inhibiteur endogène IF1 chez Saccharomyces cerevisiae. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2013PA11T097

Chicago Manual of Style (16^th Edition):

Wu, Qian. “Regulation of mitochondrial ATPase by its inhibitor protein IF1 in Saccharomyces cerevisiae : Régulation de l’ATP synthase mitochondriale par son inhibiteur endogène IF1 chez Saccharomyces cerevisiae.” 2013. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed April 14, 2021. http://www.theses.fr/2013PA11T097.

MLA Handbook (7^th Edition):

Wu, Qian. “Regulation of mitochondrial ATPase by its inhibitor protein IF1 in Saccharomyces cerevisiae : Régulation de l’ATP synthase mitochondriale par son inhibiteur endogène IF1 chez Saccharomyces cerevisiae.” 2013. Web. 14 Apr 2021.

Vancouver:

Wu Q. Regulation of mitochondrial ATPase by its inhibitor protein IF1 in Saccharomyces cerevisiae : Régulation de l’ATP synthase mitochondriale par son inhibiteur endogène IF1 chez Saccharomyces cerevisiae. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2013. [cited 2021 Apr 14]. Available from: http://www.theses.fr/2013PA11T097.

Council of Science Editors:

Wu Q. Regulation of mitochondrial ATPase by its inhibitor protein IF1 in Saccharomyces cerevisiae : Régulation de l’ATP synthase mitochondriale par son inhibiteur endogène IF1 chez Saccharomyces cerevisiae. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2013. Available from: http://www.theses.fr/2013PA11T097

27. D. Ronchi. IDENTIFICAZIONE DI UNA NUOVA CAUSA GENETICA IN UN CASO FAMILIARE DI ENCEFALOMIOPATIA MITOCONDRIALE E DEFICIT DI CITOCROMO C OSSIDASI.

Degree: 2010, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/155501

► Using a linkage whole-genome SNP genotyping, we identified a missense mutation within the GFER gene as the cause of an infantile progressive mitochondrial myopathy. The… (more)

▼ Using a linkage whole-genome SNP genotyping, we identified a missense mutation within the GFER gene as the cause of an infantile progressive mitochondrial myopathy. The human GFER (growth factor ERV1 homolog), also called ALR (augmenter of liver regeneration), belongs to the ERV1/ALR sulfhydryl oxidase family, which requires flavin adenine dinucleotide (FAD) as a cofactor. The physiological role of Erv1 has been elucidated in S. cerevisiae. ERV1 is an essential gene whose product is localized to the mitochondrial IMS. Together with Mia40, it participates in the DRS that drives the import of small IMS proteins to their final localization. Briefly, the DRS consists of two essential components: the sulfhydryl oxidase Erv1 (homolog to human GFER) and the redox-regulated import receptor Mia40. The DRS drives the import of cysteine-rich proteins into the IMS by an oxidative folding mechanism. Erv1p is reoxidized within this system, transferring its electrons onto molecular oxygen via interaction with cytochrome c and Cytochrome c Oxidase (COX), thereby linking the DRS to respiratory chain activity. Proteins belonging to the class of IMS, substrates of the DRS, are only partially identified. These include: a) small Tim proteins, chaperones involved in transport from the outer to the inner mitochondrial membrane; b) proteins involved in COX assembly; c) protein involved in protection from superoxide radicals generated by cellular respiration. The consequence of the mutation at the muscle and fibroblast levels are: 1) reduction of multiple mitochondrial respiratory chain complexes activity (predominantly Complex IV), which was restored by overexpression of the wild-type protein; 2) impaired import of human cysteine-rich proteins, known to be imported through the DRS in yeast, into mitochondria; 3) abnormal mitochondrial ultrastructural morphology, with enlargement of the IMS; 4) defective mtDNA maintenance, with accelerated time-dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces cerevisiae erv1R182H mutant strain reproduced the Complex IV activity defect and showed genetic instability of mtDNA and mitochondrial morphological defects. The aforementioned findings shed light on novel mechanisms of mitochondrial biogenesis and mtDNA maintenance, establish the role of ERV1 homologue in the human DRS, and promote the understanding of pathogenesis of a novel form of mitochondrial-related disease. Advisors/Committee Members: tutor: Giacomo Pietro Comi, COMI, GIACOMO PIETRO.

Subjects/Keywords: Mitochondrial Respiratory Chain Deficiencies; Mitochondrial Encephalomyopathies; Mitochondrial Electron Transport Chain Complex Proteins; GFER protein, human; Settore MED/26 - Neurologia

…diluite in buffer 0.1 M di sodio cacodilato, pH 7.4 (Electron Microscopy Sciences, Fort…

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APA (6^th Edition):

Ronchi, D. (2010). IDENTIFICAZIONE DI UNA NUOVA CAUSA GENETICA IN UN CASO FAMILIARE DI ENCEFALOMIOPATIA MITOCONDRIALE E DEFICIT DI CITOCROMO C OSSIDASI. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/155501

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ronchi, D.. “IDENTIFICAZIONE DI UNA NUOVA CAUSA GENETICA IN UN CASO FAMILIARE DI ENCEFALOMIOPATIA MITOCONDRIALE E DEFICIT DI CITOCROMO C OSSIDASI.” 2010. Thesis, Università degli Studi di Milano. Accessed April 14, 2021. http://hdl.handle.net/2434/155501.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ronchi, D.. “IDENTIFICAZIONE DI UNA NUOVA CAUSA GENETICA IN UN CASO FAMILIARE DI ENCEFALOMIOPATIA MITOCONDRIALE E DEFICIT DI CITOCROMO C OSSIDASI.” 2010. Web. 14 Apr 2021.

Vancouver:

Ronchi D. IDENTIFICAZIONE DI UNA NUOVA CAUSA GENETICA IN UN CASO FAMILIARE DI ENCEFALOMIOPATIA MITOCONDRIALE E DEFICIT DI CITOCROMO C OSSIDASI. [Internet] [Thesis]. Università degli Studi di Milano; 2010. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2434/155501.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ronchi D. IDENTIFICAZIONE DI UNA NUOVA CAUSA GENETICA IN UN CASO FAMILIARE DI ENCEFALOMIOPATIA MITOCONDRIALE E DEFICIT DI CITOCROMO C OSSIDASI. [Thesis]. Università degli Studi di Milano; 2010. Available from: http://hdl.handle.net/2434/155501

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. Banks, Courtney Jean. Post-Translational Regulation of Superoxide Dismutase 1 (SOD1): The Effect of K122 Acylation on SOD1's Metabolic Activity.

Degree: PhD, 2017, Brigham Young University

URL: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7941&context=etd

► Many mutations in superoxide dismutase 1 (SOD1) cause destabilization and misfolding of the protein and are implicated in amyotrophic lateral sclerosis. Likewise, a few post-translational… (more)

▼ Many mutations in superoxide dismutase 1 (SOD1) cause destabilization and misfolding of the protein and are implicated in amyotrophic lateral sclerosis. Likewise, a few post-translational modifications (PTMs) on SOD1 have been shown to cause the same phenotype. However, relatively few PTMs on SOD1 have been studied in depth and, in particular, very few studies have demonstrated how these PTMs affect SOD1's various biological roles. SOD1 is traditionally known for its role in reactive oxygen species (ROS)-scavenging but has also been found to have a few other biological roles, including transcription factor activity to promote genomic stability, preservation of cytoskeletal activity, maintaining zinc and copper homeostasis, and suppressing respiration. We have used the computational analysis tool, SAPH-ire, to find PTM 'hotspots' on SOD1 that have a high likelihood of affecting its biological functions. Interestingly, the top seven ranked PTM 'hotspots' were found in a small region of SOD1, between S98-K128. We focused our studies on one of the PTM 'hotspots' found in this region, lysine-122 (K122). K122 is found in the electrostatic loop of SOD1, a loop that is important for shuttling in superoxide radicals to be neutralized. According to our data, and other studies, this lysine is both succinylated and acetylated. We found that acetyl and succinyl-mimetics (K122Q and K122E, respectively) of this site do not affect its ROS scavenging activity but do prevent SOD1 from suppressing respiration and decrease its localization to the mitochondria. Further, when cells are depleted of SIRT5 (the desuccinylase for K122), SOD1 can no longer suppress respiration. Additionally, we found that SOD1 appears to suppress respiration at complex I, whether directly or through an indirect pathway is unknown. When HCT116 colon cancer cells were depleted of endogenous SOD1, the overexpressed succinyl K122-mimetic (K122E) could not recover growth as well as overexpressed WT SOD1. The K122E SOD1 expressing cells also exhibited increased mitochondrial ROS and unhealthier mitochondria. We propose a mechanism whereby SOD1 suppression of respiration acts as an additional regulator of oxidative stress: SOD1 suppresses the electron transport chain to decrease reactive oxygen species leakage and to promote healthier mitochondria and growth.

Subjects/Keywords: SOD1; post-translational modification; acetylation; succinylation; acylation; electron transport chain; Chemistry

…Saccharomyces cerevisiae cytochrome b2 ETC = electron transport chain 3-NP = 3-nitropropionic acid Dox… …electron transport chain (ETC) [1]. SOD1 is also important in regulating zinc… …Acylation. Lysine acylation is the addition of an acyl group with varying carbon chain lengths to… …fast axonal transport [71]. This draws a striking connection between fALS and… …and inhibit kinesin-based fast axonal transport speculated that oxidation leads to SOD1…

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APA (6^th Edition):

Banks, C. J. (2017). Post-Translational Regulation of Superoxide Dismutase 1 (SOD1): The Effect of K122 Acylation on SOD1's Metabolic Activity. (Doctoral Dissertation). Brigham Young University. Retrieved from https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7941&context=etd

Chicago Manual of Style (16^th Edition):

Banks, Courtney Jean. “Post-Translational Regulation of Superoxide Dismutase 1 (SOD1): The Effect of K122 Acylation on SOD1's Metabolic Activity.” 2017. Doctoral Dissertation, Brigham Young University. Accessed April 14, 2021. https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7941&context=etd.

MLA Handbook (7^th Edition):

Banks, Courtney Jean. “Post-Translational Regulation of Superoxide Dismutase 1 (SOD1): The Effect of K122 Acylation on SOD1's Metabolic Activity.” 2017. Web. 14 Apr 2021.

Vancouver:

Banks CJ. Post-Translational Regulation of Superoxide Dismutase 1 (SOD1): The Effect of K122 Acylation on SOD1's Metabolic Activity. [Internet] [Doctoral dissertation]. Brigham Young University; 2017. [cited 2021 Apr 14]. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7941&context=etd.

Council of Science Editors:

Banks CJ. Post-Translational Regulation of Superoxide Dismutase 1 (SOD1): The Effect of K122 Acylation on SOD1's Metabolic Activity. [Doctoral Dissertation]. Brigham Young University; 2017. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7941&context=etd

University of Illinois – Urbana-Champaign

29. Park, David S. Structural and biochemical studies on enzymes involved in natural product biosynthesis and cellular respiration.

Degree: PhD, Biophysics & Computnl Biology, 2016, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/90469

► Natural products have recently become an interest in modern research. This is due to their synthesis mainly by living organisms and their natural biosynthesis and… (more)

▼ Natural products have recently become an interest in modern research. This is due to their synthesis mainly by living organisms and their natural biosynthesis and abundance. Many of these compounds have been found to have pharmaceutical and industrial applications, and have been used as the basis for derivatives that are already being used for large scale production. Despite initial availability, there now is an urgent need to isolate and produce new and more effective natural products. The good news is we are still continuing to discover new sources. Natural products will still be an important source for industrial and pharmaceutical development. One focus improving them is to understand the biosynthetic pathways of some of these natural products. Elucidating these biosynthetic pathways will allow us to be improve efficacy and allow for rational design of new and better compounds. The studies that were conducted in this dissertation focuses on structural studies of three enzymes involved with natural product synthesis. The most widely distributed component of brown algae is alginate, a cell wall polysaccharide composed of polymeric blocks of α-(1,4) O-linked β-D-mannuronate (M) and its C-5 epimer α-L-guluronate (G). Biochemical characterization of the Saccharophagus degredans polysaccharide lyase-17 familty enzyme (Alg17c) demonstrates that the enzyme can depolymerize alginate di-, tri-, and tetra-saccharide into monosaccharides, providing the necessary precursor for ethanol fermentation. In chapter 1 we present several crystal structures of the PL-17 enzyme Alg7c from S. degredans, including the wild-type enzymes, respective mutants, and a co-crystal structure of one of the varients in complex with an alginate trisaccharide. Structure-guided analysis of several active site variants, allow for the identification of residues that are critical for substrate recognition and for the bases of the exolytic reaction mechanism of PL-17 enzymes. Plumbemycin is an antibacterial phosphonate peptide from Streptomyces plumbeus containing APPA (2-amino-5-phosphono-3-pentenoic acid), a compound that inhibits the threonine synthesis. The current pathway is unknown, but a proposed pathway has been formulated based on the pathway of a structurally similar APPA containing antifungal compound rhizocticin. There is a putative class II aldolase, PluG, in the biosynthetic pathway which is proposed to catalyze an aldol reaction between oxaloacetate and phosphonoacetaldehyde to form a reactive hydroxyl intermediate (2-keto-4-hydroxy-5-phosphonopentanoic acid), with a chance to form an irreversible, non-enzymatic dehydration reaction which forms an off pathway end product. In chapter 2, we obtained a high resolution structure of a PluG ortholog from Saccharothrix aerocolonigenes. The data from this structure shows an uncommon c-terminal domain, which we hypothesize to promote the formation of a complex with a subsequent enzyme from the plumbemycin biosynthetic pathway. We also propose that a hydrophobic tunnel forms between the two active… Advisors/Committee Members: Nair, Satish K (advisor), Nair, Satish K (Committee Chair), Gennis, Robert (committee member), Jin, Hong (committee member), Grosman, Claudio (committee member).

Subjects/Keywords: X-Ray Crystallography; Natural Products, Protein; Enzyme Structure; Drug Design; Membrane Protein; Protein Purification; Alginate Lyase; Plumbemycin; Rhizocticin; Antibiotic; Antifungal; aa3-Menaquinone Oxidase; Mining Microbial Genomics; Biofuels; Biodiesel; Enzyme Kinetics; Electron Transport Chain

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APA (6^th Edition):

Park, D. S. (2016). Structural and biochemical studies on enzymes involved in natural product biosynthesis and cellular respiration. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/90469

Chicago Manual of Style (16^th Edition):

Park, David S. “Structural and biochemical studies on enzymes involved in natural product biosynthesis and cellular respiration.” 2016. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/90469.

MLA Handbook (7^th Edition):

Park, David S. “Structural and biochemical studies on enzymes involved in natural product biosynthesis and cellular respiration.” 2016. Web. 14 Apr 2021.

Vancouver:

Park DS. Structural and biochemical studies on enzymes involved in natural product biosynthesis and cellular respiration. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2016. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/90469.

Council of Science Editors:

Park DS. Structural and biochemical studies on enzymes involved in natural product biosynthesis and cellular respiration. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/90469

University of New South Wales

30. Worgan, Lisa Catherine. The role of nuclear-encoded subunit genes in mitochondrial complex 1 deficiency.

Degree: Women's & Children's Health, 2005, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/22307 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:738/SOURCE01?view=true

► BACKGROUND: Mitochondrial complex I deficiency often leads to a devastating neurodegenerative disorder of childhood. In most cases, the underlying genetic defect is unknown. Recessive nuclear… (more)

▼ BACKGROUND: Mitochondrial complex I deficiency often leads to a devastating neurodegenerative disorder of childhood. In most cases, the underlying genetic defect is unknown. Recessive nuclear gene mutations, rather than mitochondrial DNA mutations, account for the majority of cases.AIM: Our aim was to identify the genetic basis of complex I deficiency in 34 patients with isolated complex I deficiency, by studying six of the 39 nuclear encoded complex I subunit genes (NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS7 and NDUFS8). These genes have been conserved throughout evolution and carry out essential aspects of complex I function. METHODS: RNA was extracted from patient fibroblasts and cDNA made by reverse transcription. Overlapping amplicons that together spanned the entire coding area of each gene were amplified by PCR. The genes were screened for mutations using denaturing High Performance Liquid Chromatography (dHPLC). Patient samples with abnormal dHPLC profiles underwent direct DNA sequencing. RESULTS: Novel mutations were identified in six of 34 (18%) patients with isolated complex I deficiency. Five patients had two mutations identified and one patient had a single mutation in NDUFS4 identified. All patients with mutations had a progressive encephalopathy and five out of six had Leigh syndrome or Leigh like syndrome. Mutations were found in three nuclear encoded subunit genes, NDUFV1, NDUFS2 and NDUFS4. Three novel NDUFV1 mutations were identified (R386H, K111E and P252R). The R386H mutation was found in two apparently unrelated patients. Four novel NDUFS2 mutations were identified (R221X, M292T, R333Q and IVS9+4A<G). The novel NDUFS4 mutation c.221delC was found in two patients - one in homozygous form and the other heterozygous. Specific genotype and phenotype correlations were not identified. CONCLUSIONS: Nuclear encoded complex I subunit gene mutations are an important contributor to the aetiology of isolated complex I deficiency in childhood. Screening of these genes is an essential part of the investigation of complex I deficiency.

Subjects/Keywords: Mitochondrial diseases; Respiratory chain; Electron transport Complex I; Mutation; Leigh disease; Mitochondrial pathology; Genetic aspects; Genetic disorders in children

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Worgan, L. C. (2005). The role of nuclear-encoded subunit genes in mitochondrial complex 1 deficiency. (Masters Thesis). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/22307 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:738/SOURCE01?view=true

Chicago Manual of Style (16^th Edition):

Worgan, Lisa Catherine. “The role of nuclear-encoded subunit genes in mitochondrial complex 1 deficiency.” 2005. Masters Thesis, University of New South Wales. Accessed April 14, 2021. http://handle.unsw.edu.au/1959.4/22307 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:738/SOURCE01?view=true.

MLA Handbook (7^th Edition):

Worgan, Lisa Catherine. “The role of nuclear-encoded subunit genes in mitochondrial complex 1 deficiency.” 2005. Web. 14 Apr 2021.

Vancouver:

Worgan LC. The role of nuclear-encoded subunit genes in mitochondrial complex 1 deficiency. [Internet] [Masters thesis]. University of New South Wales; 2005. [cited 2021 Apr 14]. Available from: http://handle.unsw.edu.au/1959.4/22307 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:738/SOURCE01?view=true.

Council of Science Editors:

Worgan LC. The role of nuclear-encoded subunit genes in mitochondrial complex 1 deficiency. [Masters Thesis]. University of New South Wales; 2005. Available from: http://handle.unsw.edu.au/1959.4/22307 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:738/SOURCE01?view=true

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