DHODH tangoing with GPX4 on the ferroptotic stage

Ferroptosis, an iron-dependent form of regulated cell death, is prevented by activity of the glutathione-dependent phospholipid hydroperoxidase GPX4 (Glutathione peroxidase 4) in the cytosol and mitochondria, and by the glutathione-independent CoQ10 oxidoreductase FSP1 at the plasma membrane. In their recent paper published in Nature , Mao et al. report that DHODH (Dihydroorotate dehydrogenase) coordinates with GPX4 to block ferroptosis in the mitochondrial inner membrane by reducing ubiquinone to form ubiquinol in cancer cells, thus providing a novel targeted strategy for treating cancer. 1