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In the first step, GPx is oxidized by hydroperoxides

p53 activates the LOX enzyme ALOX12 to induce ferroptosis in cells independent of GPX4 activity (Ou et al., 2016)

7 Notably, the ALOX12 inhibitor ML355 robustly ameliorated I/R-induced organ injury in mouse, swine, and monkey models, suggesting a promising use for pharmaceutically targeting ALOX12 in I/R injury treatment