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Overview
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PDHK3 or Pyruvate Dehydrogenase Kinase 3 is a member of the PDHK family that phosphorylate and inactivate the Pyruvate Dehydrogenase (PDH). PDH is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. HIF-1 induces PDHK3 expression leading to inhibition of mitochondrial respiration. Forced expression of PDHK3 in cancer cells results in increased lactic acid accumulation and drugs resistance, whereas knocking down PDHK3 inhibits hypoxia-induced cytoplasmic glycolysis and cell survival.
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