The mitochondrial pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that convert pyruvate into acetyl-CoA. Pyruvate dehydrogenase (E1) (PDH; EC 1.2.4.1) is the first component enzyme of PDC that controls glycolysis-derived pyruvate entry into the tricarboxylic acid (TCA) cycle where it can be oxidized to support ATP generation or its carbon diverted to anabolism. The activity of PDH (E1) is rapidly regulated by phosphorylation and dephosphorylation events that are catalyzed by PDH kinases (PDKs 1-4) and PDH phosphatases (PDPs), respectively. Phosphorylation of PDH results in inhibition of activity, whereas, dephosphorylation increases it[1]. Besides a crucial role in patients that suffer from pyruvate dehydrogenase deficiency –one of the most common neurodegenerative disorders associated with abnormal mitochondrial metabolism–  PDH is also topic of interest of many studies on cancer. In cancer cells pyruvate is abundantly transformed to lactate, regardless of the presence of oxygen. This phenomenon, known historically as the Warburg effect, is called aerobic glycolysis. The biologic basis of this intensified glycolysis and shift of pyruvate transformation to lactate in cancer cells is thought to be related to HIF1α[2].