In collaboration with Jean-Claude Martinou we were involved in the identification of mitochondrial pyruvate carrier, which imports pyruvate into the mitochondrial matrix, ending a 40-year search.
Figure: Comparative model of the mitochondrial pyruvate carrier based on the distantly related semiSWEET transporter of Vibrio.
In mammalians the mitochondrial pyruvate carrier consists of two protomers MPC1 and MPC2, each predicted to form a membrane protein with three transmembrane α-helices (blue, yellow and red) and a N-terminal amphipathic α-helix (white). Only co-expression of MPC1 and MPC2 in the cytoplasmic membrane of Lactococcus lactis results in uptake of pyruvate in whole cells, which could be inhibited by the specific inhibitor UK5099 . The carrier is distantly related to the semiSWEET transporters of bacteria, which are homo-dimers involved in sugar uptake . A dysfunctional mitochondrial pyruvate carrier causes mitochondrial disease with lactic acidosis and hyperpyruvatemia .
We are interested in studying the mitochondrial pyruvate carrier, because many questions remain with respect to its structure, oligomeric state, kinetic properties, transport mechanism, physiological role and involvement in disease .
- (2012) Identification and functional expression of the mitochondrial pyruvate carrier. Science 337, 93-6
- (2014) Structures of bacterial homologues of SWEET transporters in two distinct conformations. Nature 515, 448-52
- (2012) A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science 337, 96-100
- (2015) Mitochondrial pyruvate import and its effects on homeostasis. Curr Opin Cell Biol 33, 35-41