The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis
Open accessAbstract
Significance: Ferroptosis is a regulated form of cell death induced by loss of glutathione peroxidase 4 (GPX4) phospholipid peroxidase activity and lethal accumulation of reactive oxygen species. Small-molecule inhibitors of GPX4 induce ferroptosis; however, the interaction between these inhibitors and GPX4 has remained elusive, as has the identity of the reactive oxygen species that drive execution of ferroptosis. We identified here a ligand-binding site on GPX4 and determined the specific lipids oxidized during ferroptosis. We further identified two key drivers of lipid peroxidation during ferroptosis: lipoxygenases and phosphorylase kinase G2. These findings reveal a previously enigmatic mechanism of ferroptotic lipid peroxide generation and suggest new strategies for pharmacological control of ferroptosis and diseases associated with this mode of cell death.
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“the ferroptosis-inhibiting effect of iron depletion by either chelators [539, 543, 548] or phosphorylase kinase catalytic subunit gamma 2 (PHKG2) knockdown [566]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [566]
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“In the context of ferroptosis, PUFA peroxidation seems to be mainly regulated by the mutually antagonistic activity of LOXs (which directly catalyze lipid peroxidation) and GPX4 (which indirectly inhibits it) [550, 566].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [566]
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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
Self-citationRegulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
Self-citationInactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Self-citationPrinciples of bioactive lipid signalling: lessons from sphingolipids
Hannun, Y. A., & Obeid, L. M. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2329 · Cited by 3,411
Ferroptosis as a p53-mediated activity during tumour suppression
Jiang, L., Kon, N., Li, T., Wang, S.-J., Su, T., Hibshoosh, H., Baer, R., & Gu, W. (2015) · Nature · doi:10.1038/nature14344 · Cited by 3,398
Dixon, S. J., Patel, D. N., Welsch, M., Skouta, R., Lee, E. D., Hayano, M., Thomas, A. G., Gleason, C. E., Tatonetti, N. P., Slusher, B. S., et al. (2014) · eLife · doi:10.7554/elife.02523 · Cited by 2,088
Self-citationYang, W. S., & Stockwell, B. R. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.02.010 · Cited by 1,876
Self-citationA Lentiviral RNAi Library for Human and Mouse Genes Applied to an Arrayed Viral High-Content Screen
Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., Piqani, B., Eisenhaure, T., Luo, B., Grenier, J. K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.040 · Cited by 1,804
Self-citationRAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels
Yagoda, N., von Rechenberg, M., Zaganjor, E., Bauer, A. J., Yang, W. S., Fridman, D. J., Wolpaw, A. J., Smukste, I., Peltier, J. M., Boniface, J. J., et al. (2007) · Nature · doi:10.1038/nature05859 · Cited by 1,631
Self-citationLentivirus-delivered stable gene silencing by RNAi in primary cells.
Stewart, S. A., Dykxhoorn, D. M., Palliser, D., Mizuno, H., Yu, E. Y., An, D., Sabatini, D., Chen, I. S. Y., Hahn, W., Sharp, P., et al. (2003) · RNA: A publication of the RNA Society · doi:10.1261/rna.2192803 · Cited by 1,619
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Ferroptosis: 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
Self-citationFerroptosis: mechanisms, biology and role in disease
Jiang, X., Stockwell, B. R., & Conrad, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00324-8 · Cited by 7,973
Self-citationGalluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Ferroptosis: molecular mechanisms and health implications
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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
Metadata
- Authors
- Yang, W. S., Kim, K. J., Gaschler, M. M., Patel, M., Shchepinov, M. S., & Stockwell, B. R.
- Affiliations
- St. John's University (US)
- Columbia University (US)
- New York University (US)
- Retrotope (United States) (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-08-09
- Volume
- 113
- Issue
- 34
- Pages
- E4966-75
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5003261
- OpenAlex
- W2508296626
- Cited by
- 2,329
- References
- 60
- Citations by year
- 2026: 230 · 2025: 348 · 2024: 441 · 2023: 410 · 2022: 319 · 2021: 249 · 2020: 152 · 2019: 70 · 2018: 62 · 2017: 36 · 2016: 7
- FWCI
- 52.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA097061)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Keywords
- ferroptosis, lipid peroxidation, polyunsaturated fatty acids, lipoxygenase, GPX4, iron availability, selenocysteine, deuterated fatty acids, reactive oxygen species, non-apoptotic cell death
- MeSH terms
- Phospholipid Hydroperoxide Glutathione Peroxidase, Deuterium, Epithelial Cells, Fatty Acids, Unsaturated, Gene Expression Regulation, Glutathione Peroxidase, Humans, Iron, Lipid Peroxides, Phosphorylase Kinase, Recombinant Fusion Proteins, Lipid Peroxidation, Signal Transduction, Cell Death, Selenocysteine, Catalytic Domain, Protein Transport, Cell Line, Tumor, Green Fluorescent Proteins, Lipoxygenases
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