Abstract
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 (H(2)O(2)). H(2)O(2) 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.