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Description

At the level of ferroptosis, hypoxia inhibits lipid peroxidation through a dual mechanism: 1) HIF-1/2 upregulates PLIN2, a lipid droplet-associated protein, forming a physical barrier to isolate peroxidation reaction substrates (Zou et al., 2020) (215)

Second, modulating key lipid-metabolizing enzymes, especially ACSL4, reduces PUFA incorporation into membrane phospholipids, lowering the substrate pool for lipid peroxidation and decreasing ferroptosis susceptibility