The pyruvate dehydrogenase complex in cancer: An old metabolic gatekeeper regulated by new pathways and pharmacological agents

Int J Cancer. 2016 Feb 15;138(4):809-17. doi: 10.1002/ijc.29564. Epub 2015 Apr 28.

Abstract

Cancer cells exhibit an altered metabolism which is characterized by a preference for aerobic glycolysis more than mitochondrial oxidation of pyruvate. This provides anabolic support and selective growth advantage for cancer cells. Recently, a new concept has arisen suggesting that these metabolic changes may be due, in part, to an attenuated mitochondrial function which results from the inhibition of the pyruvate dehydrogenase complex (PDC). This mitochondrial complex links glycolysis to the Krebs cycle and the current understanding of its regulation involves the cyclic phosphorylation and dephosphorylation by specific pyruvate dehydrogenase kinases (PDKs) and pyruvate dehydrogenase phosphatases (PDPs).

Keywords: PDK inhibitors; Warburg effect; cancer metabolism; pyruvate dehydrogenase complex; pyruvate dehydrogenase kinase; pyruvate dehydrogenase phosphatase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Mitochondria / metabolism
  • Neoplasms / metabolism*
  • Pyruvate Dehydrogenase Complex / metabolism*

Substances

  • Pyruvate Dehydrogenase Complex