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Our recent study showed that two oxidoreductases – NADPH-cytochrome P450 reductase (POR) and NADH-cytochrome b5 reductase (CYB5R1) – transfer electrons to oxygen to generate hydrogen peroxide (H2O2). H2O2 then reacts with ferrous iron, generating hydroxyl radicals that cause peroxidation of polyunsaturated-fatty-acid chains of membrane phospholipids, resulting in plasma membrane rupture and ferroptosis.