Ferroptosis is a regulated form of cell death driven by iron dependent lipid peroxidation. Unlike apoptosis or necrosis, it is defined by catastrophic damage to polyunsaturated phospholipids in cellular membranes, triggered when antioxidant defenses fail and redox active iron is abundant.

A central protective system is the cystine glutamate antiporter system xc− that imports cystine for glutathione synthesis. Glutathione serves as a cofactor for glutathione peroxidase 4 GPX4, an enzyme that reduces toxic lipid hydroperoxides to non toxic lipid alcohols. Inhibition of system xc− or GPX4 depletes glutathione or blocks detoxification, allowing lipid peroxides to accumulate until membranes lose integrity and ferroptosis ensues. This can be induced by small molecules such as erastin that targets system xc− or direct GPX4 inhibitors.

Iron promotes ferroptosis by catalyzing Fenton type reactions that convert peroxides into highly reactive radicals, and by supporting specific lipoxygenases that oxygenate polyunsaturated fatty acids in membranes. Cellular iron import, storage, and export pathways therefore strongly influence ferroptosis sensitivity. Conversely, ferroptosis can be suppressed by iron chelators, radical trapping antioxidants, and enzymes such as ferroptosis suppressor protein 1 that use alternative reducing systems to limit lipid peroxidation.

Ferroptosis plays roles in diverse contexts. It contributes to ischemia reperfusion injury in organs such as brain, heart, and kidney, and is implicated in neurodegenerative diseases where iron and oxidative stress accumulate. In cancer, many therapy resistant cells show heightened ferroptosis sensitivity, suggesting that inducing ferroptosis might overcome resistance. Ongoing research aims to map ferroptosis regulatory networks, identify biomarkers, and develop both ferroptosis inducers as anticancer agents and inhibitors as protectants in degenerative and ischemic diseases.