The oxidoreductases POR and CYB5R1 catalyze lipid peroxidation to execute ferroptosis
Youwei Ai, Bo Yan, Xiaodong Wang
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 (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.
Topics & Concepts
Hydrogen peroxideLipid peroxidationChemistryCytochrome b5FerrousReductasePolyunsaturated fatty acidBiochemistryRadicalGPX4Cytochrome cCytochrome P450 reductaseMembraneCytochromeEnzymeFatty acidCoenzyme Q – cytochrome c reductaseOrganic chemistryMitochondrionCatalaseGlutathione peroxidasePeroxisome Proliferator-Activated ReceptorsMetabolomics and Mass Spectrometry StudiesDrug Transport and Resistance Mechanisms