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.
The net process is denoted by:
:ADP + ATP → ADP + ATP
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 translocator cycles between two states, called the cytoplasmic and matrix state, opening up to these compartments in an alternating way. There are structures available that show the translocator locked in a cytoplasmic state by the inhibitor carboxyatractyloside, or in the matrix state by the inhibitor bongkrekic acid.