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Duke University

1. Ding, Chien-Kuang Cornelia. Regulation of Ferroptosis by a novel NADPH phosphatase MESH1 .

Degree: 2019, Duke University

Ferroptosis is a form of regulated cell death featured by lipid peroxidation and breakage of cell membrane. However, the molecular mediators and regulators are not fully understood. Here, we identified the metazoan homologues of ppGpp hydrolase (MESH1) is an efficient cytosolic NADPH phosphatase, an unexpected enzymatic activity that is captured by the crystal structure of the MESH1-NADPH complex. Ferroptosis elevates MESH1, whose upregulation depletes NADPH and sensitizes cells to ferroptosis. Conversely, MESH1 depletion rescues ferroptosis by sustaining the levels of NADPH and GSH and by reducing lipid peroxidation. Importantly, the ferroptotic protection by MESH1 depletion is ablated by suppression of the cytosolic NAD(H) kinase, NADK, but not its mitochondrial counterpart NADK2. MESH1 depletion also triggers extensive transcriptional changes that are distinct from the canonical integrated stress response, but show striking similarity to the bacterial stringent response. MESH1 depletion also leads to dNTP depletion and inhibition of cell proliferation in tumor cells. Finally, we established Mesh1 knockout mouse model to study the physiological relevance of MESH1. Advisors/Committee Members: Chi, Jen-Tsan A (advisor).

Subjects/Keywords: Biochemistry; Molecular biology; Ferroptosis; HDDC3; MESH1; NADPH

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

APA (6th Edition):

Ding, C. C. (2019). Regulation of Ferroptosis by a novel NADPH phosphatase MESH1 . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/18658

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):

Ding, Chien-Kuang Cornelia. “Regulation of Ferroptosis by a novel NADPH phosphatase MESH1 .” 2019. Thesis, Duke University. Accessed January 19, 2020. http://hdl.handle.net/10161/18658.

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

MLA Handbook (7th Edition):

Ding, Chien-Kuang Cornelia. “Regulation of Ferroptosis by a novel NADPH phosphatase MESH1 .” 2019. Web. 19 Jan 2020.

Vancouver:

Ding CC. Regulation of Ferroptosis by a novel NADPH phosphatase MESH1 . [Internet] [Thesis]. Duke University; 2019. [cited 2020 Jan 19]. Available from: http://hdl.handle.net/10161/18658.

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

Council of Science Editors:

Ding CC. Regulation of Ferroptosis by a novel NADPH phosphatase MESH1 . [Thesis]. Duke University; 2019. Available from: http://hdl.handle.net/10161/18658

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

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