PerspectiveCell Biology

A Mitochondrial Mystery, Solved

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Science  06 Jul 2012:
Vol. 337, Issue 6090, pp. 41-43
DOI: 10.1126/science.1225601

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The three-carbon molecule pyruvate is a metabolic intermediate and a central hub for cellular energy metabolism. It lies at the junction of aerobic and anaerobic metabolism and is the precursor for biosynthetic pathways including glucose, lipid, and amino acid syntheses. Given the ubiquitous role of pyruvate in cellular bioenergetics (see the figure), its subcellular localization plays a critical role in its fate. The final product of pyruvate metabolism is fundamentally altered once it enters the mitochondrion. As such, the identity of the protein that transports pyruvate from the cytoplasm into mitochondria has been eagerly anticipated, and the wait has been nearly 40 years. Two papers in this issue, by Bricker et al. (1) on page 96 and Herzig et al. on page 93 (2), report the identification of a mitochondrial pyruvate carrier (MPC) responsible for this function—a momentous development in the field of bioenergetics with profound implications for treating metabolic diseases.