LMS Seminar – Edmund Kunji
“Refuelling the eukaryotic cell: how ADP and ATP cross the mitochondrial inner membrane”
The mitochondrial carrier family (SLC25) has 53 members in humans, transporting nucleotides, carboxylates, amino acids, fatty acids, vitamins and inorganic ions across the mitochondrial inner membrane for many key processes in the cell. The mitochondrial ADP/ATP carrier (SLC25A4), also called adenine nucleotide translocase, imports the spent fuel ADP into the mitochondrial matrix for ATP synthesis, and exports ATP from the mitochondrion to fuel cellular activities. In the transport cycle, the carrier changes between a cytoplasmic and matrix state, in which the central substrate binding site is alternately accessible to these compartments. A structure of a cytoplasmic state was known, but recently, a structure of a matrix state in complex with bongkrekic acid was solved. Comparison of the two states explains the function of highly conserved sequence features and reveals that the transport mechanism is unique, involving the coordinated movement of six dynamic elements around a central translocation pathway, which is universal for all mitochondrial carriers.
MRC Mitochondria Unit, Cambridge