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Cell biology

Ferroptosis

DEFerroptose

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Ferroptosis is a form of regulated cell death driven by iron-dependent accumulation of lipid peroxides to lethal levels, distinguishing it mechanistically from apoptosis, necroptosis and pyroptosis. The key regulatory node is glutathione peroxidase 4 (GPX4), which uses the antioxidant glutathione to reduce phospholipid hydroperoxides; when GPX4 activity is insufficient — due to glutathione depletion, GPX4 inhibition or excess labile iron — unreduced lipid peroxides propagate chain reactions that disrupt membrane integrity. Ferroptosis has been implicated in neurodegeneration, ischaemia-reperfusion injury and cancer cell death, and its relevance to tissue ageing is an active area of research, particularly in the context of declining GPX4 expression and iron accumulation observed with age.

Sources

  1. Dixon et al.. (2012). Ferroptosis: an iron-dependent form of nonapoptotic cell death. *Cell*doi:10.1016/j.cell.2012.03.042
  2. Stockwell et al.. (2017). Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. *Cell*doi:10.1016/j.cell.2017.09.021