The Mitochondrial Pyruvate Carrier and Metabolic Regulation

Abstract

Pyruvate is a key intermediate at the branchpoint of anaerobic and aerobic energy metabolism. Its transport into the mitochondrial matrix is necessary prior to its decarboxylation into acetyl-CoA, which feeds the reducing equivalent-generating tricarboxylic acid (TCA) cycle. Although the existence of specific carrier transport of cytosolic pyruvate into the mitochondria has been inferred from a myriad of studies, the identities of the mitochondrial pyruvate carrier (MPC) were only confirmed very recently. Identification of the MPC facilitated several other recent advances. These include the finding of MPC’s inhibition by the insulin-sensitizing drug family thiazolidinediones, how cells respond flexibly to a reduction in MPC functionality, as well as insights into how changes in MPC levels affect oncogenic potential of cancer cells. These new findings, discussed here in this brief review, have important implications in therapeutic approaches towards metabolic disorders and cancer.