Fig. 6

The role of PUFAs in ferroptosis. PUFAs are acetylated by acyl-CoA synthetase and integrated into phospholipids (LPs). The PUFAs containing PLs are oxidized through the non-enzymatic Fenton reaction or enzymatic peroxidation by LOXs, COXs and CYPs. The peroxidation of PUFAs can be inhibited by ferrostatins, liproxstatins, vitamin E, CoQ₁₀ and BH₄, and lipid peroxides can be reduced to the corresponding alcohol by GPX4. The lipid peroxides exert cytotoxicity by altering lipid-lipid interactions, membrane permeability, ion gradients and membrane fluidity, and their degradation products (mainly hydroxy acids and reactive aldehydes) can from crosslinks with proteins or DNA