ATP–ADP translocase

ADP/ATP translocases, also known as adenine nucleotide translocases (ANT) and ADP/ATP carrier proteins (AAC), are transporter proteins that enable the exchange of cytosolic adenosine diphosphate (ADP) and mitochondrial adenosine triphosphate (ATP) across the inner mitochondrial membrane. Free ADP is transported from the cytoplasm to the mitochondrial matrix, while ATP produced from oxidative phosphorylation is transported from the mitochondrial matrix to the cytoplasm, thus providing the cells with its main energy currency. ADP/ATP translocases, also known as adenine nucleotide translocases (ANT) and ADP/ATP carrier proteins (AAC), are transporter proteins that enable the exchange of cytosolic adenosine diphosphate (ADP) and mitochondrial adenosine triphosphate (ATP) across the inner mitochondrial membrane. Free ADP is transported from the cytoplasm to the mitochondrial matrix, while ATP produced from oxidative phosphorylation is transported from the mitochondrial matrix to the cytoplasm, thus providing the cells with its main energy currency. ADP/ATP translocases are exclusive to eukaryotes and are thought to have evolved during eukaryogenesis. Human cells express four ADP/ATP translocases: SLC25A4, SLC25A5, SLC25A6 and SLC25A31, which constitute more than 10% of the protein in the inner mitochondrial membrane. These proteins are classified under the mitochondrial carrier superfamily. ADP/ATP translocase 1 is the major AAC in human cells and the archetypal protein of this family. It has a mass of approximately 30 kDa, consisting of 297 residues. It forms six transmembrane α-helices that form a barrel that results in a deep cone-shaped depression accessible from the outside where the substrate binds. The binding pocket, conserved throughout most isoforms, mostly consists of basic residues that allow for strong binding to ATP or ADP and has a maximal diameter of 20 Å and a depth of 30 Å. Indeed, arginine residues 96, 204, 252, 253, and 294, as well as lysine 38, have been shown to be essential for transporter activity. Under normal conditions, ATP and ADP cannot cross the inner mitochondrial membrane due to their high negative charges, but ADP/ATP translocase, an antiporter, couples the transport of the two molecules. The depression in ADP/ATP translocase alternatively faces the matrix and the cytoplasmic sides of the membrane. ADP in the intermembrane space, coming from the cytoplasm, binds the translocase and induces its eversion, resulting in the release of ADP into the matrix. Binding of ATP from the matrix induces eversion and results in the release of ATP into the intermembrane space, subsequently diffusing to the cytoplasm, and concomitantly brings the translocase back to its original conformation. ATP and ADP are the only natural nucleotides recognized by the translocase.