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Either the overproduction of the Fe 2+ that is involved in the formation of lipid hydroperoxides through the Fenton reaction 111 or the inactivation of glutathione peroxidase 4, which is programmed to degrade lipid hydroperoxides, leads to intracellular lipid hydroperoxide accumulation to a lethal level, ultimately triggering ferroptosis 112

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Given the cytosolic NADPH depletion in shGDH1 cells, we wondered whether -KG insufficiency affects AMPK activation