Figure 2.

Regulation of lipid peroxidation in ferroptosis. In the presence of Fe²⁺, hydrogen peroxide can generate hydroxyl radicals (OH⁻) through the fenton reaction, thereby promoting the oxidation of PUFAs on the cell membrane. ACSL4 incorporates PUFAs into the membrane as PUFA-CoA, and LPCAT3 inserts the acyl group into the lysophospholipid as PUFA-PE, of which will lead to the accumulation of PE-PUFA-OOH and in turn generate multiple aldehydes including 4-HNE. PE-PUFA-OOH can be repaired by GPX4 to reduce lipid hydrogen peroxide to protect the membrane function, and FIN56 can reverse the process through inhibiting GPX4.