In 1955, Siekevitz and Potter demonstrated that adenine nucleotides were distributed in cells in two pools located in the mitochondrial and cytosolic compartments. Shortly thereafter, Pressman hypothesized that the two pools could exchange nucleotides. 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.
Soon after, an overwhelming amount of research was done in proving the existence and elucidating the link between ADP/ATP translocase and energy transport. cDNA of ADP/ATP translocase was sequenced for bovine in 1982 and a yeast species Saccharomyces cerevisiae in 1986 before finally Battini et al. sequenced a cDNA clone of the human transporter in 1989. The homology in the coding sequences between human and yeast ADP/ATP translocase was 47% while bovine and human sequences extended remarkable to 266 out of 297 residues, or 89.6%. In both cases, the most conserved residues lie in the ADP/ATP substrate binding pocket.