PDK4 and cancer: Pyruvate dehydrogenase kinase 4 (PDK4) isoform is a gatekeeping enzyme that negatively phosphorylates pyruvate dehydrogenase, leading to conversion of pyruvate to lactate in the cytoplasm instead of further oxidation in mitochondria (i.e. OXPHOS).9 PDK4 is mostly detected in the skeletal muscle and heart,10 and its overexpression has been reported in glioblastoma, breast11 and colon12 cancers.