The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers
Open accessAbstract
Cancer cells rewire their metabolism and rely on endogenous antioxidants to mitigate lethal oxidative damage to lipids. However, the metabolic processes that modulate the response to lipid peroxidation are poorly defined. Using genetic screens, we compared metabolic genes essential for proliferation upon inhibition of cystine uptake or glutathione peroxidase-4 (GPX4). Interestingly, very few genes were commonly required under both conditions, suggesting that cystine limitation and GPX4 inhibition may impair proliferation via distinct mechanisms. Our screens also identify tetrahydrobiopterin (BH4) biosynthesis as an essential metabolic pathway upon GPX4 inhibition. Mechanistically, BH4 is a potent radical-trapping antioxidant that protects lipid membranes from autoxidation, alone and in synergy with vitamin E. Dihydrofolate reductase catalyzes the regeneration of BH4, and its inhibition by methotrexate synergizes with GPX4 inhibition. Altogether, our work identifies the mechanism by which BH4 acts as an endogenous antioxidant and provides a compendium of metabolic modifiers of lipid peroxidation. Genetic screens reveal a compendium of metabolic modifiers of lipid peroxidation. Tetrahydrobiopterin is essential under GPX4 inhibition, acting as a radical-trapping antioxidant that inhibits lipid peroxidation and is regenerated by DHFR.
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Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
Regulation of Ferroptotic Cancer Cell Death by GPX4
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ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
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The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
Bersuker, K., Hendricks, J. M., Li, Z., Magtanong, L., Ford, B., Tang, P. H., Roberts, M. A., Tong, B., Maimone, T. J., Zoncu, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1705-2 · Cited by 3,703
MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis
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FSP1 is a glutathione-independent ferroptosis suppressor
Doll, S., Freitas, F. P., Shah, R., Aldrovandi, M., da Silva, M. C., Ingold, I., Goya Grocin, A., Xavier da Silva, T. N., Panzilius, E., Scheel, C. H., et al. (2019) · Nature · doi:10.1038/s41586-019-1707-0 · Cited by 3,341
Self-citationOxidized arachidonic and adrenic PEs navigate cells to ferroptosis
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CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
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Cited by
Targeting Ferroptosis as a Vulnerability in Cancer
Lei, G., Zhuang, L., & Gan, B. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00459-0 · Cited by 2,252
The Cell Biology of Ferroptosis
Dixon, S. J., & Olzmann, J. A. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00703-5 · Cited by 1,596
Ferroptosis: Mechanisms and links with diseases
Yan, H.-F., Zou, T., Tuo, Q.-Z., Xu, S., Li, H., Belaidi, A. A., & Lei, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00428-9 · Cited by 1,471
Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones
Liang, D., Feng, Y., Zandkarimi, F., Wang, H., Zhang, Z., Kim, J., Cai, Y., Gu, W., Stockwell, B. R., & Jiang, X. (2023) · Cell · doi:10.1016/j.cell.2023.05.003 · Cited by 722
Ferroptosis in cancer and cancer immunotherapy
Zhao, L., Zhou, X., Xie, F., Zhang, L., Yan, H., Huang, J., Zhang, C., Zhou, F., Chen, J., & Zhang, L. (2022) · Cancer Communications · doi:10.1002/cac2.12250 · Cited by 684
Metadata
- Authors
- Soula, M., Weber, R. A., Zilka, O., Alwaseem, H., La, K., Yen, F., Molina, H., Garcia-Bermudez, J., Pratt, D. A., & Birsoy, K.
- Venue
- Nature Chemical Biology
- Published
- 2020-08-10
- Volume
- 16
- Issue
- 12
- Pages
- 1351-1360
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W3048885175
- Cited by
- 732
- References
- 58
- FWCI
- 39.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Soula, M., Weber, R. A., Zilka, O., Alwaseem, H., La, K., Yen, F., Molina, H., Garcia-Bermudez, J., Pratt, D. A., & Birsoy, K. (2020). Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers. Nature Chemical Biology. https://doi.org/10.1038/s41589-020-0613-y
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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