Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis

By W. Yang, Katherine J. Kim, M. Gaschler, Milesh Patel, M. Shchepinov, Brent R. Stockwell. Proceedings of the National Academy of Sciences of the United States of America, 2016

2,092 citations recorded by the source corpus.

Subfields: Immunology, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/d77d7339b44f4b01a7348a2676b5fa3fe3b18174

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Citations in the corpus

Multi-stage differentiation defines melanoma subtypes with differential vulnerability to drug-induced iron-dependent oxidative stress (2018, background): “In addition to GSH levels, differential levels of cellular iron, iron-dependent lipoxygenases, and oxidizable polyunsaturated fatty acids in the lipid membrane could all contribute to the differences in ferroptosis sensitivity (Dixon et al., 2012; Yang et al., 2016).”
GPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues (2017, neutral): “Hence, data showing an anti-ferroptotic effect by either deleting a distinctive lipoxygenase ( i.e ., 15-LOX) (98) or knocking down one or several LOX isoforms (120) are currently restricted to the cellular level and need validation in an in vivo relevant setting.”
Autophagy-Dependent Ferroptosis: Machinery and Regulation (2020, background): “, 2016b) and lipoxygenase (arachidonate lipoxygenase [ALOX]) enzymes (Yang et al., 2016).”
Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis. (2017, neutral): “Of notice,Gpx4cys/cys cells were even more resistant to ferroptosis-inducing agents (Figure S4D), mainly due to increased GSH levels (Figure S4E) and decreased nucleophilicity of the catalytic thiolate compared to selenolate (Figure S4F) (Yang et al., 2016).”
FINO2 Initiates Ferroptosis Through GPX4 Inactivation and Iron Oxidation (2018, neutral): “The observation that FINO 2 caused decreased GPX4 activity suggested that, like RSL3, FINO 2 might be a direct inhibitor of GPX4 4, 6 , or that FINO 2 could deplete GPX4 protein, similar to the ferroptosis inducer FIN56.”
Ferroptosis: mechanisms and links with diseases (2021, background): “The oxidation of the formed PE-AA may follow either enzymatically through the action of Lox, or non-enzymatically through autoxidation to form PE-AA-OOH, both of which ultimately causes cell death.(1,38,45,46) It has been reported that this reaction may occur on the mitochondrial membrane(1) or the ”
Neuronal Cell Death. (2018, neutral): “Ferroptosis appears to require the iron-dependent lipid peroxidation of polyunsaturated fatty acids, and although the mechanisms that result in necrosis downstream of lipid peroxidation remain unclear, they may involve AIF release from mitochondria and nuclear translocation (530, 613, 761).”
Inhibition of neuronal ferroptosis protects hemorrhagic brain. (2017, methodology): “To further verify the presence of ferroptosis in Hb-treated OHSCs and ICH brain in vivo, we tested a second, independent ferroptosis inhibitor, liproxstatin-1, and the arachidonate lipoxygenase (ALOX) inhibitor zileuton, which has also been shown to inhibit ferroptosis (35).”