The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
GPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues
Open accessAbstract
SIGNIFICANCE: Iron-dependent lipid peroxidation is a complex oxidative process where phospholipid hydroperoxides (PLOOH) are produced in membranes and finally transformed into a series of decomposition products, some of which are endowed with biological activity. It is specifically prevented by glutathione peroxidase 4 (GPx4), the selenoenzyme that reduces PLOOH by glutathione (GSH). PLOOH is both a product and the major initiator of peroxidative chain reactions, as well as an activator of lipoxygenases. α-Tocopherol both specifically breaks peroxidative chain propagation and inhibits lipoxygenases. Thus, GPx4, GSH, and α-tocopherol are integrated in a concerted anti-peroxidant mechanism. Recent Advances: Ferroptosis has been recently identified as a cell death subroutine that is specifically activated by missing GPx4 activity and inhibited by iron chelation or α-tocopherol supplementation. Ferroptosis induction may underlie spontaneous human diseases, such as major neurodegeneration and neuroinflammation, causing an excessive cell death. The basic mechanism of ferroptosis, therefore, fits the features of activation of lipid peroxidation. CRITICAL ISSUES: Still lacking are convincing proofs that lipoxygenases are involved in ferroptosis. Also, unknown are the molecules eventually killing cells and the mechanisms underlying the drop of the cellular anti-peroxidant capacity. FUTURE DIRECTIONS: Molecular events and mechanisms of ferroptosis to be unraveled and validated on animal models are GPx4 inactivation, role of GSH concentration, increased iron availability, and membrane structure and composition. This is expected to drive drug discovery that is aimed at halting cell death in degenerative diseases or boosting it in cancer cells. Antioxid. Redox Signal. 29, 61-74.
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Cites
Regulation 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
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
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
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-citationFerroptosis 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
The Pecking Order of Free Radicals and Antioxidants: Lipid Peroxidation, α-Tocopherol, and Ascorbate
Buettner, G. R. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1074 · Cited by 2,417
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
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148
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
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Cited by
Role of GPX4 in ferroptosis and its pharmacological implication
Seibt, T. M., Proneth, B., & Conrad, M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.014 · Cited by 1,520
Self-citationGTP Cyclohydrolase 1/Tetrahydrobiopterin Counteract Ferroptosis through Lipid Remodeling
Kraft, V. A. N., Bezjian, C. T., Pfeiffer, S., Ringelstetter, L., Müller, C., Zandkarimi, F., Merl-Pham, J., Bao, X., Anastasov, N., Kössl, J., et al. (2020) · ACS Central Science · doi:10.1021/acscentsci.9b01063 · Cited by 1,298
13 reasons why the brain is susceptible to oxidative stress
Cobley, J. N., Fiorello, M. L., & Bailey, D. M. (2018) · Redox Biology · doi:10.1016/j.redox.2018.01.008 · Cited by 1,215
The molecular and metabolic landscape of iron and ferroptosis in cardiovascular disease
Fang, X., Ardehali, H., Min, J., & Wang, F. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00735-4 · Cited by 1,081
Li, Y., Feng, D., Wang, Z., Zhao, Y., Sun, R., Tian, D., Liu, D., Zhang, F., Ning, S., Yao, J., et al. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-019-0299-4 · Cited by 872
Metadata
- Authors
- Maiorino, M., Conrad, M., & Ursini, F.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2018-07
- Volume
- 29
- Issue
- 1
- Pages
- 61-74
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W2611610643
- Cited by
- 703
- References
- 31
- FWCI
- 18.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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