The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals
Open accessAbstract
SUMMARY Ferroptosis is a form of programmed cell death pathogenic to several acute and chronic diseases and executed via oxygenation of polyunsaturated phosphatidylethanolamines (PE) by 15-lipoxygenases (15-LO) that normally use free polyunsaturated fatty acids as substrates. Mechanisms of the altered 15-LO substrate specificity are enigmatic. We sought a common ferroptosis regulator for 15LO. We discovered that PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 and 15LO2, and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis. We demonstrated the importance of PEBP1-dependent regulatory mechanisms of ferroptotic death in airway epithelial cells in asthma, kidney epithelial cells in renal failure and cortical and hippocampal neurons in brain trauma. As master regulators of ferroptotic cell death with profound implications for human disease, PEBP1/15LO complexes represent a new target for drug discovery.
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Metadata
- Authors
- Wenzel, S. E., Tyurina, Y. Y., Zhao, J., St. Croix, C. M., Dar, H. H., Mao, G., Tyurin, V. A., Anthonymuthu, T. S., Kapralov, A. A., Amoscato, A. A., Mikulska-Ruminska, K., Shrivastava, I. H., Kenny, E. M., Yang, Q., Rosenbaum, J. C., Sparvero, L. J., Emlet, D. R., Wen, X., Minami, Y., Qu, F., Watkins, S. C., Holman, T. R., VanDemark, A. P., Kellum, J. A., Bahar, I., Bayır, H., & Kagan, V. E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 171
- Issue
- 3
- Pages
- 628-641.e26
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2759112714
- Cited by
- 950
- References
- 10
- FWCI
- 34.02
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Wenzel, S. E., Tyurina, Y. Y., Zhao, J., St. Croix, C. M., Dar, H. H., Mao, G., Tyurin, V. A., Anthonymuthu, T. S., Kapralov, A. A., Amoscato, A. A., Mikulska-Ruminska, K., Shrivastava, I. H., Kenny, E. M., Yang, Q., Rosenbaum, J. C., Sparvero, L. J., Emlet, D. R., Wen, X., Minami, Y., . . . Kagan, V. E. (2017). PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell. https://doi.org/10.1016/j.cell.2017.09.044
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
