The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Plasticity of ether lipids promotes ferroptosis susceptibility and evasion
Open accessAbstract
Ferroptosis—an iron-dependent, non-apoptotic cell death process—is involved in various degenerative diseases and represents a targetable susceptibility in certain cancers1. The ferroptosis-susceptible cell state can either pre-exist in cells that arise from certain lineages or be acquired during cell-state transitions2–5. However, precisely how susceptibility to ferroptosis is dynamically regulated remains poorly understood. Here we use genome-wide CRISPR–Cas9 suppressor screens to identify the oxidative organelles peroxisomes as critical contributors to ferroptosis sensitivity in human renal and ovarian carcinoma cells. Using lipidomic profiling we show that peroxisomes contribute to ferroptosis by synthesizing polyunsaturated ether phospholipids (PUFA-ePLs), which act as substrates for lipid peroxidation that, in turn, results in the induction of ferroptosis. Carcinoma cells that are initially sensitive to ferroptosis can switch to a ferroptosis-resistant state in vivo in mice, which is associated with extensive downregulation of PUFA-ePLs. We further find that the pro-ferroptotic role of PUFA-ePLs can be extended beyond neoplastic cells to other cell types, including neurons and cardiomyocytes. Together, our work reveals roles for the peroxisome–ether-phospholipid axis in driving susceptibility to and evasion from ferroptosis, highlights PUFA-ePL as a distinct functional lipid class that is dynamically regulated during cell-state transitions, and suggests multiple regulatory nodes for therapeutic interventions in diseases that involve ferroptosis. The cellular organelles peroxisomes contribute to the sensitivity of cells to ferroptosis by synthesizing polyunsaturated ether phospholipids, and changes in the abundances of these lipids are associated with altered sensitivity to ferroptosis during cell-state transitions.
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Regulation of Ferroptotic Cancer Cell Death by GPX4
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Self-citationFerroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2239 · Cited by 4,293
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
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
Defining a Cancer Dependency Map
Tsherniak, A., Vazquez, F., Montgomery, P. G., Weir, B. A., Kryukov, G., Cowley, G. S., Gill, S., Harrington, W. F., Pantel, S., Krill-Burger, J. M., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.010 · Cited by 3,276
Genesis and development of DPPH method of antioxidant assay
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Ferroptosis as a target for protection against cardiomyopathy
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Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway
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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
Gerstberger, S., Jiang, Q., & Ganesh, K. (2023) · Cell · doi:10.1016/j.cell.2023.03.003 · Cited by 913
Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies
Zhou, Q., Meng, Y., Li, D., Yao, L., Le, J., Liu, Y., Sun, Y., Zeng, F., Chen, X., & Deng, G. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01769-5 · Cited by 890
Metadata
- Authors
- Zou, Y., Henry, W. S., Ricq, E. L., Graham, E. T., Phadnis, V. V., Maretich, P., Paradkar, S., Boehnke, N., Deik, A. A., Reinhardt, F., Eaton, J. K., Ferguson, B., Wang, W., Fairman, J., Keys, H. R., Dančík, V., Clish, C. B., Clemons, P. A., Hammond, P. T., Boyer, L. A., Weinberg, R. A., & Schreiber, S. L.
- Venue
- Nature
- Published
- 2020-09-16
- Volume
- 585
- Issue
- 7826
- Pages
- 603-608
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3087176574
- Cited by
- 834
- References
- 40
- FWCI
- 47.41
- Type
- journal article
- Language
- en
- Open access
- green
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- Zou, Y., Henry, W. S., Ricq, E. L., Graham, E. T., Phadnis, V. V., Maretich, P., Paradkar, S., Boehnke, N., Deik, A. A., Reinhardt, F., Eaton, J. K., Ferguson, B., Wang, W., Fairman, J., Keys, H. R., Dančík, V., Clish, C. B., Clemons, P. A., Hammond, P. T., . . . Schreiber, S. L. (2020). Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Nature. https://doi.org/10.1038/s41586-020-2732-8
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