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University of Western Ontario

1. Mathers, Katherine E. Regulation of liver mitochondrial metabolism during hibernation by post-translational modification.

Degree: 2017, University of Western Ontario

Hibernation, characterized by a seasonal reduction in metabolism and body temperature, allows animals to conserve energy when environmental conditions (e.g. temperature, food availability) are unfavourable. During hibernation, small mammals such as the 13-lined ground squirrel (Ictidomys tridecemlineatus) cycle between two distinct metabolic states: torpor, where metabolic rate is suppressed by >95% and body temperature falls to ~5 °C, and interbout euthermia (IBE), where metabolic rate and body temperature rapidly increase and are maintained at euthermic levels several hours. Suppression of metabolism during entrance into torpor is paralleled by rapid suppression of liver mitochondrial metabolism. In my thesis, I aimed to characterize the regulatory mechanisms that underlie this rapid and reversible mitochondrial suppression. Using high resolution respirometry and enzymatic assays, I determined that this suppression between IBE and torpor occurs at electron transport system (ETS) complexes I and II. Flux through complexes I and II is suppressed during torpor by 40% and 60%, respectively, despite no differences in protein content between the two hibernation states. I used two-dimensional differential gel electrophoresis and Blue-Native PAGE to determine if differences in post-translational modification of mitochondrial proteins parallels these metabolic changes. I found that the 75 kDa subunit of complex I is significantly more phosphorylated in torpor than IBE, and that the complex II flavoprotein subunit is significantly more phosphorylated in IBE than torpor. To investigate the potential that this differential phosphorylation mediates the observed differences in enzyme activity and mitochondrial metabolism between torpor and IBE, I attempted to manipulate phosphorylation state of complexes I and II as well as stimulate the endogenous protein kinase A (PKA) pathway within intact liver mitochondria. I found that dephosphorylation of complex I reversed suppression of its activity during torpor, and that dephosphorylation of complex II induced suppression of its activity in IBE. I was unable to stimulate the endogenous PKA within intact mitochondria, and suggest that another pathway is responsible for mediating changes in phosphorylation in vivo. Together, my results point to novel ETS phosphorylation sites that may contribute to metabolic regulation in general and, in particular, suppression of mitochondrial metabolism during hibernation.

Subjects/Keywords: Hibernation; metabolism; post-translational modification; phosphorylation; electron transport system; metabolic suppression; Biochemistry; Biology; Cellular and Molecular Physiology; Zoology

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

APA (6th Edition):

Mathers, K. E. (2017). Regulation of liver mitochondrial metabolism during hibernation by post-translational modification. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/5098

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

Chicago Manual of Style (16th Edition):

Mathers, Katherine E. “Regulation of liver mitochondrial metabolism during hibernation by post-translational modification.” 2017. Thesis, University of Western Ontario. Accessed June 18, 2018. https://ir.lib.uwo.ca/etd/5098.

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

MLA Handbook (7th Edition):

Mathers, Katherine E. “Regulation of liver mitochondrial metabolism during hibernation by post-translational modification.” 2017. Web. 18 Jun 2018.

Vancouver:

Mathers KE. Regulation of liver mitochondrial metabolism during hibernation by post-translational modification. [Internet] [Thesis]. University of Western Ontario; 2017. [cited 2018 Jun 18]. Available from: https://ir.lib.uwo.ca/etd/5098.

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

Council of Science Editors:

Mathers KE. Regulation of liver mitochondrial metabolism during hibernation by post-translational modification. [Thesis]. University of Western Ontario; 2017. Available from: https://ir.lib.uwo.ca/etd/5098

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

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