The long and winding road to the mitochondrial pyruvate carrier

The extraction of energy and biosynthetic building blocks from fuel metabolism is a fundamental requisite for life. Through the action of cellular enzymes, complex carbon structures are broken down in reactions coupled to the production of high-energy phosphates as in ATP and GTP as well as electron carriers such as NADH and FADH(2). These processes traverse across compartments inside the cell in order to access specific enzymes and environments. Pyruvate is the end product of cytosolic glycolysis and has a variety of possible fates, the major one being mitochondrial oxidation. While this metabolite has been known to cross the inner mitochondrial membrane for decades, it is only recently that proteins necessary for this activity have been identified. This review will chronicle more than 40 years of research interrogating this critical process and will discuss some of the possible implications of this discovery for cancer metabolism.