Fig. 5
The role of iron in the generation of cellular oxygen radicals and lipid peroxidation. Superoxide dismutase (SOD) catalyses the dismutation of the superoxide (O2-) radical into oxygen (O2) and hydrogen peroxide (H2O2). Ferrous iron (Fe2+) is oxidized to ferric iron (Fe3+) through reaction with hydrogen peroxide (H2O2), to produce highly reactive hydroxyl radicals (OH·), which is termed the Fenton reaction. RH (refer to PUFA-PL) is attacked by HO· and forms R·, which then react with O2 into R-OO·. R-OO· reacts with another RH to produce R· and R-OOH. R-OOH is an oxidation product, which can also be derived from RH catalysed by LOXs. GPX4, the vital anti-ferroptotic factor, reduces R-OOH into nontoxic R-OH. In the presence of Fe3+ or Fe2+, R-OOH forms R-OO· or R-O·, respectively. The latter reacts with another RH to produce R-OH and R·. In this process, R· (labelled by a blue frame) and R-OO· (labelled by a red frame) are continuously generated and contribute to the amplification of oxygen radicals and lipid peroxidation production