Ferroptosis

Ferroptosis inducers and inhibitors are used to study an iron-dependent form of regulated cell death. The term was introduced in 2012 for erastin-triggered cell death that differs from apoptosis and requires iron. Erastin depletes glutathione by inhibiting system xc-, the cystine/glutamate antiporter that supplies cysteine to cells. Glutathione peroxidase 4 (GPX4) reduces phospholipid hydroperoxides, and its inhibition lets lipid peroxidation accumulate to lethal levels. RSL3 and ML-210 inhibit GPX4 directly and are standard inducers in cell models. Ferrostatin-1 and liproxstatin-1 act in the opposite direction by trapping lipid radicals. Liproxstatin-1 protected mice with inducible Gpx4 deletion from acute renal failure in a 2014 study. Iron chelators such as deferiprone help to confirm the iron dependence of the process.