The role of monounsaturated fatty acids in ferroptosis
Abstract/Contents
- Abstract
- Ferroptosis is an iron-dependent, oxidative form of cell death that is a result of toxic accumulation of polyunsaturated fatty acid phospholipid hydroperoxides (PUFA-PL-OOH). This death can occur upon inhibition of the phospholipid glutathione peroxidase, GPX4. I find here that cancer cell lines are not uniformly reliant on GPX4 for cell survival. A compendium of factors drives GPX4 essentiality including PUFA content within cells but also reliance on de novo MUFA biogenesis. This work reveals novel MUFAs that can inhibit ferroptosis. Protective MUFAs lead to decreased abundance of toxic PUFA-PLs which reduces ferroptotic stress in cancer cells. I also find that ASCL3, which is required for oleic acid to protect from ferroptosis, is required for some but not all MUFAs to protect from ferroptosis. I identify a novel player in MUFA metabolism, MBOAT2, which prevents cells from using MUFAs to prevent ferroptosis. Finally, I discover that oleic acid can become less protective against ferroptosis when FSP1 is inhibited, depending on the cell line context. Overall, these findings suggest there is a complex machinery within cells that metabolizes MUFAs and complicates our view of how ferroptosis pathways interact.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Pope, Lauren Elizabeth |
|---|---|
| Degree supervisor | Dixon, Scott James, 1977- |
| Thesis advisor | Dixon, Scott James, 1977- |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Long, Jonathan Z |
| Thesis advisor | Morrison, Ashby J |
| Degree committee member | Bassik, Michael |
| Degree committee member | Long, Jonathan Z |
| Degree committee member | Morrison, Ashby J |
| Associated with | Stanford University, School of Humanities and Sciences |
| Associated with | Stanford University, Department of Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Lauren Elizabeth Pope. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/yv064kn6328 |
Access conditions
- Copyright
- © 2023 by Lauren Elizabeth Pope
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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