Structural changes in the transport cycle of the mitochondrial ADP/ATP carrier

[Display omitted] •First structure of the matrix-open state of a mitochondrial ADP/ATP carrier has been solved.•Structure determined using protein inhibited by the toxin bongkrekic acid, which blocks the substrate-binding site.•Structural comparison shows highly dynamic conformational changes during transport with six mobile elements.•Proposed mechanism explains roles of all conserved sequence features in mitochondrial carriers. The mitochondrial ADP/ATP carrier, also called adenine nucleotide translocase, accomplishes one of the most important transport activities in eukaryotic cells, importing ADP into the mitochondrial matrix for ATP synthesis, and exporting ATP 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.