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As the core antagonist of lipid peroxidation, GPX4 converts toxic lipid hydroperoxides (L-OOH) into inert lipid alcohols (L-OH) by consuming the reducing power provided by GSH, effectively blocking the propagation of radical chain reactions ( - ) ( - ( 2.4 The critical role of mitochondria in ferroptosis As a core regulatory hub of ferroptosis, mitochondrial dynamic structural and functional disorders run through the entire process of ferroptosis ( 2.5 The dynamic regulatory network of ferroptosis signaling pathways 2.5.1 Oxidative stress response pathway Nrf2, as the central hub of antioxidant defense, binds to Keap1 and is continuously degraded in a resting state ( - , leading to the interruption of GSH synthesis and the inactivation of GPX4 (38).It is worth noting that post-translational modifications (such as acetylation) or subtype-selective splicing of p53 can dynamically regulate its pro-death activity, revealing its complex regulatory hierarchy in the oxidative stress response (39)
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