PDK1 and cancer: This is mostly due to the defective transport of pyruvate from cytoplasm into the mitochondrial matrix because of the cancer-associated downregulation of the pyruvate-carrier components MPC1 and MPC2 in the inner mitochondrial membrane [30] and the decreased catalytic activity of PDH due to an increased expression of PDH kinase-1 (PDK-1) and PDH kinase-3 (PDK-3) and consequent increased phosphorylation of PDH [31].