Systematic identification of regulators of oxidative stress reveals non-canonical roles for peroxisomal import and the pentose phosphate pathway
Abstract/Contents
- Abstract
- Reactive oxygen species play critical roles in metabolism and disease, yet a comprehensive analysis of cellular response to oxidative stress is lacking. To systematically identify genetic factors that control this response, we conducted genome-wide Cas9/CRISPR and shRNA screens. We find that, paradoxically, disrupting the pentose phosphate pathway (PPP) at the level of phosphogluconate dehydrogenase (PGD) protects cells against ROS. This dramatically alters metabolites in the PPP, consistent with rewiring of upper glycolysis to promote antioxidant production. In addition, we found that disruption of the peroxisomal import pathway unexpectedly increases resistance to oxidative stress by altering the intracellular localization of canonical ROS scavenger, catalase. In addition to these counterintuitive findings, these results reveal a detailed picture of diverse pathways that control oxidative stress response, which range from components of the TCA cycle and DNA repair machineries to iron transport, trafficking and metabolism. Together, these studies provide new insights into the roles of the peroxisomal matrix import pathway and the pentose phosphate pathway in redox biology, and represent a rich resource for understanding the cellular response to oxidative stress.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Dubreuil, Michael Mayne |
|---|---|
| Degree supervisor | Bassik, Michael |
| Degree supervisor | Dixon, Scott James, 1977- |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Dixon, Scott James, 1977- |
| Thesis advisor | Jackson, Peter K. (Peter Kent) |
| Thesis advisor | Pfeffer, Suzanne |
| Degree committee member | Jackson, Peter K. (Peter Kent) |
| Degree committee member | Pfeffer, Suzanne |
| Associated with | Stanford University, Cancer Biology Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Michael Mayne Dubreuil. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Michael Dubreuil
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...