The metabolic checkpoint of ferroptosis remains obscure. We find that glucose favors system xc- inhibitor-induced ferroptosis by activating pyruvate oxidation, thereby promoting fatty acid synthesis and subsequent lipid peroxidation. In contrast, the upregulation of pyruvate dehydrogenase kinase 4 (PDK4) switches into a ferroptosis-resistant state in pancreatic cancer cells.
Keywords: Ferroptosis; fatty acid synthesis; metabolic basis; pancreatic cancer; pyruvate oxidation.
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