Journal
MEDICAL HYPOTHESES
Volume 101, Issue -, Pages 69-74Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.mehy.2017.02.017
Keywords
Ferroptosis; Cell death; Oxidative stress; Iron toxicity; Glutathione depletion; Free radicals
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Funding
- National Sciences and Engineering Research Council of Canada (NSERC) [460639-2014]
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Ferroptosis is a recently discovered form of regulated necrosis that involves iron-dependent lipid peroxidation. How cells die once ferroptosis is triggered remains unclear. Ferroptosis is hypothesized to require three critical events: (1) accumulation of redox-active iron, (2) glutathione depletion, and (3) lipid per oxidation. It is proposed that these three events must unfold simultaneously because stopping any critical event also stops ferroptosis. These events are hypothesized to amplify in severity through positive feedback loops. The cause of death in ferroptosis is therefore the synergistic combination of antioxidant depletion, iron toxicity, and membrane denaturation. The relevance of these feedback loops for cancer and neurodegenerative therapies is discussed. (C) 2017 Elsevier Ltd. All rights reserved.
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