Meta-Biol

• Pathways

Pyruvate (PYR) and a proton (H+) are cotransported from the mitochondrial intermembrane space to the mitochondrial matrix, mediated by a complex of mitochondrial pyruvate carriers 1 and 2 (MCP1 and MCP2) located in the inner mitochondrial membrane (McCommis & Finck 2015). The proton gradient across the inner mitochondrial membrane must be maintained for ATP production to occur. Transport of PYR across this membrane would collapse this gradient therefore PYR is cotransported with H+. Studies of pyruvate uptake in rat indicate that it is specific, saturable, and competitively inhibitable, indicating a specific role for a membrane transport protein (Papa et al. 1971, Halestrap & Denton 1974), and the stoichiometry of the human reaction is inferred from this work. MCP1 and MCP2 have been identified as essential components of the transporter based on the observation that expression of both proteins (but not either one alone) restored mitochondrial pyruvate uptake in mutant budding yeast. The proteins form a multimeric complex; its stoichiometry is unknown (Bricker et al. 2012).