Computational and Experimental Definition of a Consensus Ferroptosis Regulatory Network
Abstract/Contents
- Abstract
- Ferroptosis is a form of non-apoptotic regulated cell death associated with an accumulation of lipid reactive oxygen species (ROS). The genetic regulation of ferroptosis is not clearly understood. Several important regulators of ferroptosis have been identified previously, but the picture is still not complete as there are disagreements between published genetic screens about what genes are important. Here, we assemble a complete network of what is known about genetic regulators of ferroptosis. The research includes data mining and in vitro work. The data mining consisted of a literature search for all ferroptosis genetic screens, combining all of the data to construct a ferroptosis regulatory network. A clear divide in genetic regulators of ferroptosis via direct GPX4 inhibition and regulators of ferroptosis via system xc- inhibition emerged in the network. In vitro, cells were transiently transfected to reintroduce ACSL4, the most highly connected gene in the network, demonstrating that ACSL4 is required for death by GPX4 inhibition and providing a framework for future research into other highly connected genes. The network also demonstrated this genetic separation, with ACSL4 shown as a key gene required for death by GPX4 inhibitors but not by system xc- inhibitors. This work demonstrates that there is a clear separation of genetic regulators of the two pathways of death by ferroptosis and indicates the need for future work into understanding this separation.
Description
| Type of resource | text |
|---|---|
| Date created | June 2021 |
| Date modified | December 5, 2022 |
| Publication date | April 30, 2022 |
Creators/Contributors
| Author | Mueller, Grace D. |
|---|---|
| Degree granting institution | Stanford University, Department of Biology, 2021 |
| Thesis advisor | Dixon, Scott J. |
| Thesis advisor | Morrison, Ashby J. |
Subjects
| Subject | Biology |
|---|---|
| Subject | Ferroptosis |
| Subject | Genetic Regulators |
| Subject | Cell Death |
| Subject | ACSL4 |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
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- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred citation
- Mueller, Grace D., Dixon, Scott J., and Morrison, Ashby J. (2021). Computational and Experimental Definition of a Consensus Ferroptosis Regulatory Network. Stanford Digital Repository. Available at: https://purl.stanford.edu/qj487wq8782
Collection
Undergraduate Theses, Department of Biology, 2020-2021
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- muellerg@stanford.edu
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