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Cell Death
Metazoans
Ferroptosis
Iron-dependent regulated cell death driven by lipid peroxidation.
Overview
Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxides. It occurs when the glutathione-dependent lipid repair enzyme GPX4 is inactivated or when cellular cystine import via system Xc⁻ is inhibited. Polyunsaturated fatty acids (PUFAs) in membrane phospholipids are oxidized by lipoxygenases and iron-catalyzed Fenton chemistry, leading to membrane damage.
Cellular Location
Membrane phospholipids, cytoplasm
Clinical Significance
Implicated in neurodegeneration, kidney injury, and cancer; therapy-resistant cancer cells may be vulnerable to ferroptosis inducers; GPX4 is a key drug target.