Metabolic checkpoint of ferroptosis resistance.

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.