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Unsolved mysteries: How does lipid peroxidation cause ferroptosis?
Open accessAbstract
Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes-glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases.
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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
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
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
Self-citationACSL4 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
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
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
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
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
Self-citationDixon, 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-citationDrug-tolerant persister cancer cells are vulnerable to GPX4 inhibition
Hangauer, M. J., Viswanathan, V. S., Ryan, M. J., Bole, D., Eaton, J. K., Matov, A., Galeas, J., Dhruv, H. D., Berens, M. E., Schreiber, S. L., et al. (2017) · Nature · doi:10.1038/nature24297 · Cited by 1,799
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Dodson, M., Castro-Portuguez, R., & Zhang, D. D. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101107 · Cited by 2,435
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
Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis
Su, L.-J., Zhang, J.-H., Gomez, H., Murugan, R., Hong, X., Xu, D., Jiang, F., & Peng, Z.-Y. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/5080843 · Cited by 2,166
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
The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression
Lei, G., Zhang, Y., Koppula, P., Liu, X., Zhang, J., Lin, S. H., Ajani, J. A., Xiao, Q., Liao, Z., Wang, H., et al. (2020) · Cell Research · doi:10.1038/s41422-019-0263-3 · Cited by 1,318
Zhou, N., & Bao, J. (2020) · Database · doi:10.1093/database/baaa021 · Cited by 788
Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects
Ru, Q., Li, Y., Chen, L., Wu, Y., Min, J., & Wang, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01969-z · Cited by 724
RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer
Sui, X., Zhang, R., Liu, S., Duan, T., Zhai, L., Zhang, M., Han, X., Xiang, Y., Huang, X., Lin, H., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01371 · Cited by 703
Ferroptosis in cancer and cancer immunotherapy
Zhao, L., Zhou, X., Xie, F., Zhang, L., Yan, H., Huang, J., Zhang, C., Zhou, F., Chen, J., & Zhang, L. (2022) · Cancer Communications · doi:10.1002/cac2.12250 · Cited by 684
Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators
Kajarabille, N., & Latunde-Dada, G. O. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194968 · Cited by 668
Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death
Kapralov, A. A., Yang, Q., Dar, H. H., Tyurina, Y. Y., Anthonymuthu, T. S., Kim, R., St. Croix, C. M., Mikulska-Ruminska, K., Liu, B., Shrivastava, I. H., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-019-0462-8 · Cited by 650
Yang, F., Xiao, Y., Ding, J.-H., Jin, X., Ma, D., Li, D.-Q., Shi, J.-X., Huang, W., Wang, Y.-P., Jiang, Y.-Z., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.021 · Cited by 624
Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases
Nakamura, T., Naguro, I., & Ichijo, H. (2019) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2019.06.010 · Cited by 523
Ferroptosis occurs through an osmotic mechanism and propagates independently of cell rupture
Riegman, M., Sagie, L., Galed, C., Levin, T., Steinberg, N., Dixon, S. J., Wiesner, U., Bradbury, M. S., Niethammer, P., Zaritsky, A., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0565-1 · Cited by 474
Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1
Beatty, A., Singh, T., Tyurina, Y. Y., Tyurin, V. A., Samovich, S., Nicolas, E., Maslar, K., Zhou, Y., Cai, K. Q., Tan, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22471-y · Cited by 268
Lytic cell death in metabolic liver disease
Gautheron, J., Gores, G. J., & Rodrigues, C. M. P. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.04.001 · Cited by 225
“The reactions involving iron and leading to the hydroxyl or alkoxyl (RO ̇) radical are traditionally called Fenton reactions [54].”
BackgroundPLA2G6 guards placental trophoblasts against ferroptotic injury
Beharier, O., Tyurin, V. A., Goff, J. P., Guerrero-Santoro, J., Kajiwara, K., Chu, T., Tyurina, Y. Y., St Croix, C. M., Wallace, C. T., Parry, S., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2009201117 · Cited by 198
APR-246 induces early cell death by ferroptosis in acute myeloid leukemia
Birsen, R., Larrue, C., Decroocq, J., Johnson, N., Guiraud, N., Gotanegre, M., Cantero-Aguilar, L., Grignano, E., Huynh, T., Fontenay, M., et al. (2021) · Haematologica · doi:10.3324/haematol.2020.259531 · Cited by 182
Mechanism and Intervention Measures of Iron Side Effects on the Intestine
Qi, X., Zhang, Y., Guo, H., Hai, Y., Luo, Y., & Yue, T. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2019.1630599 · Cited by 142
Wu, Y., Torabi, S.-F., Lake, R. J., Hong, S., Yu, Z., Wu, P., Yang, Z., Nelson, K., Guo, W., Pawel, G. T., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade7622 · Cited by 91
MLL4 mediates differentiation and tumor suppression through ferroptosis
Egolf, S., Zou, J., Anderson, A., Simpson, C. L., Aubert, Y., Prouty, S., Ge, K., Seykora, J. T., & Capell, B. C. (2021) · Science Advances · doi:10.1126/sciadv.abj9141 · Cited by 88
Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature
Hooglugt, A., van der Stoel, M. M., Boon, R. A., & Huveneers, S. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.612802 · Cited by 82
Placental Hypoxia-Induced Ferroptosis Drives Vascular Damage in Preeclampsia
Park, C., Alahari, S., Ausman, J., Liu, R., Nguyen, F., Sallais, J., Post, M., & Caniggia, I. (2025) · Circulation Research · doi:10.1161/circresaha.124.325119 · Cited by 69
Tan, X., Huang, X., Niu, B., Guo, X., Lei, X., & Qu, B. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1102158 · Cited by 40
Dihydroxy‐Metabolites of Dihomo‐γ‐linolenic acid drive ferroptosis‐mediated neurodegeneration
Sarparast, M., Pourmand, E., Hinman, J., Vonarx, D., Reason, T., Zhang, F., Paithankar, S., Chen, B., Borhan, B., Watts, J. L., et al. (2023) · ACS Central Science · doi:10.1021/acscentsci.3c00052 · Cited by 33
Zhao, C., Pu, Z., Gao, J., Liu, C., Xing, J., Lang, W., Chen, J., Yuan, C., & Zhou, C. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c05595 · Cited by 26
Bienassis, C., Vivar, O. I., Hu, Y., Da silva, J., Darmon, A., Marill, J., Anesary, N. M., Schmitt, P., Levy, L., Welsh, J., et al. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03579-1 · Cited by 9
Metadata
- Authors
- Feng, H., & Stockwell, B. R.
- Venue
- PLOS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-05-24
- Volume
- 16
- Issue
- 5
- Pages
- e2006203
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2803347838
- Cited by
- 759
- References
- 20
- FWCI
- 37.37
- Type
- journal article
- Language
- en
- Open access
- gold
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