[13] ADP/ATP translocase transports ATP synthesized from oxidative phosphorylation into the cytoplasm, where it can be used as the principal energy currency of the cell to power thermodynamically unfavorable reactions.

Because a human typically exchanges the equivalent of their own mass of ATP on a daily basis, ADP/ATP translocase is an important transporter protein with major metabolic implications.

[1] Transport is fully reversible, and its directionality is governed by the concentrations of its substrates (ADP and ATP inside and outside mitochondria), the chelators of the adenine nucleotides, and the mitochondrial membrane potential.

[19] 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.

[8] The net process is denoted by: ADP/ATP exchange is energetically expensive: about 25% of the energy yielded from electron transfer by aerobic respiration, or one hydrogen ion, is consumed to regenerate the membrane potential that is tapped by ADP/ATP translocase.

The major morphological hallmark of MM is ragged, red fibers containing peripheral and intermyofibrillar accumulations of abnormal mitochondria.

[22][23] In particular, autosomal dominant progressive external ophthalmoplegia (adPEO) is a common disorder associated with dysfunctional ADP/ATP translocase and can induce paralysis of muscles responsible for eye movements.

The high affinity (Kd in the nanomolar range) makes each inhibitor a deadly poison by obstructing cellular respiration/energy transfer to the rest of the cell.

[21] In 1955, Siekevitz and Potter demonstrated that adenine nucleotides were distributed in cells in two pools located in the mitochondrial and cytosolic compartments.

[26] However, the existence of an ADP/ATP transporter was not postulated until 1964 when Bruni et al. uncovered an inhibitory effect of atractyloside on the energy-transfer system (oxidative phosphorylation) and ADP binding sites of rat liver mitochondria.