Ferroptosis is a regulated form of cell death driven by iron dependent lipid peroxidation. Unlike apoptosis or necrosis, it is characterized by catastrophic damage to polyunsaturated phospholipids in cellular membranes, culminating in loss of membrane integrity and cell collapse.

A central protective system against ferroptosis is the glutathione peroxidase 4 (GPX4) pathway. Cysteine imported through the system xC- transporter is used to synthesize glutathione, which GPX4 requires to detoxify lipid hydroperoxides. Inhibition of system xC- or GPX4 depletes this defense, allowing iron catalyzed reactions to oxidize membrane lipids and trigger ferroptosis.

Lipid composition strongly influences susceptibility. Enzymes that incorporate polyunsaturated fatty acids into phospholipids promote ferroptosis, while saturation of membrane lipids or upregulation of antioxidant pathways confers resistance. Mitochondria and other organelles can modulate sensitivity by shaping cellular redox status and metabolic flux.

Research links ferroptosis to multiple diseases. In cancer, many tumors are vulnerable to ferroptosis induction, and combining ferroptosis inducers with conventional therapies can overcome resistance. In contrast, in neurodegenerative and ischemic diseases, unwanted ferroptosis of neurons or other sensitive cells contributes to pathology, making ferroptosis inhibition a therapeutic goal.

Emerging regulators include p53, NRF2 and distinct metabolic and signaling networks that integrate stress responses, iron handling and lipid metabolism. Small molecules that either trigger or block ferroptosis are being developed and optimized.

Overall, ferroptosis research is uncovering how iron, lipids and redox biology intersect in cell fate decisions and is providing new therapeutic angles for both killing diseased cells and preserving vulnerable tissues.