The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase
Open accessAbstract
Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity.
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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
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
Inactivation 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
Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis
Yang, W. S., Kim, K. J., Gaschler, M. M., Patel, M., Shchepinov, M. S., & Stockwell, B. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603244113 · Cited by 2,329
Yang, W. S., & Stockwell, B. R. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.02.010 · Cited by 1,876
Seiler, A., Schneider, M., Förster, H., Roth, S., Wirth, E. K., Culmsee, C., Plesnila, N., Kremmer, E., Rådmark, O., Wurst, W., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.07.005 · Cited by 1,470
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Resolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis
Shah, R., Shchepinov, M. S., & Pratt, D. A. (2018) · ACS Central Science · doi:10.1021/acscentsci.7b00589 · Cited by 782
Do Van, B., Gouel, F., Jonneaux, A., Timmerman, K., Gelé, P., Pétrault, M., Bastide, M., Laloux, C., Moreau, C., Bordet, R., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.05.011 · Cited by 689
T cell lipid peroxidation induces ferroptosis and prevents immunity to infection
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Cited by
GPX4 at the crossroads of lipid homeostasis and ferroptosis
Forcina, G. C., & Dixon, S. J. (2019) · PROTEOMICS · doi:10.1002/pmic.201800311 · Cited by 1,025
The emerging role of ferroptosis in inflammation
Sun, Y., Chen, P., Zhai, B., Zhang, M., Xiang, Y., Fang, J., Xu, S., Gao, Y., Chen, X., Sui, X., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110108 · Cited by 739
Richards, S. E. V., Yang, M., Deik, A. A., & Ricq, E. L. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04463-2 · Cited by 3
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Metadata
- Authors
- Hinman, A., Holst, C. R., Latham, J. C., Bruegger, J. J., Ulas, G., McCusker, K. P., Amagata, A., Davis, D., Hoff, K. G., Kahn-Kirby, A. H., Kim, V., Kosaka, Y., Lee, E., Malone, S. A., Mei, J. J., Richards, S. J., Rivera, V., Miller, G., Trimmer, J. K., & Shrader, W. D.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-08-15
- Volume
- 13
- Issue
- 8
- Pages
- e0201369
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2885747263
- Cited by
- 189
- References
- 12
- FWCI
- 10.31
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hinman, A., Holst, C. R., Latham, J. C., Bruegger, J. J., Ulas, G., McCusker, K. P., Amagata, A., Davis, D., Hoff, K. G., Kahn-Kirby, A. H., Kim, V., Kosaka, Y., Lee, E., Malone, S. A., Mei, J. J., Richards, S. J., Rivera, V., Miller, G., Trimmer, J. K., & Shrader, W. D. (2018). Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. PLOS ONE. https://doi.org/10.1371/journal.pone.0201369
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