UC San Diego

The Mitochondrial Pyruvate Carrier (MPC) family of eukaryotic protein transporters reside in the mitochondrial inner-membrane and are the essential for the 150kDa transport complex of pyruvate into the mitochondrial matrix for cellular respiration. Studies in this paper show evidence that the two primary isoforms of the family, MPC1 and MPC2, both have 3-TMS topologies. Exploration of family homologies resulted in a relationship to the bidirectional sugar transporter (SWEET) family and by extension the Transporter/Opsin/G- protein (TOG) superfamily. The two families share a 41- residue sequence motif with high sequence conservation. Binary sequence alignments using the program GSAT allowed for confirmation of the 3 TMSs of MPC aligning with the corresponding 3-TMSs of SWEET family proteins. Comparisons to the TOG superfamily show MPC evolved from the N-terminal TMS loss on the 4-TMS TOG precursor protein. Family sequence analysis also resulted in the discovery of four novel fusion proteins consisting of MPC1 and MPC2 domains to form a predicted functional pyruvate transport unit. These 6-TMS fusion proteins arose from a novel evolutionary pathway dissimilar than the other discovered TOG superfamily pathways. MPC familial homology between SWEET and other TOG superfamily proteins may help to elucidate its transport mechanism in future studies