Defining the interactome of human adenine nucleotide translocases

Adenine nucleotide translocases (ANT in mammals, AAC in yeast) mediate the 1:1 electrogenic exchange of ADP into and ATP out of the mitochondrial matrix and is thus a required component of the oxidative phosphorylation machinery. Originally modeled to function in isolation, the major isoform in Saccharomyces cerevisiae, AAC2, was recently demonstrated to associate with a number of protein complexes, including other mitochondrial solute carriers, higher order respiratory complexes (termed supercomplexes), and itself. As very little is known about the mammalian ANT interactome, we sought to define it using a proteomics-based approach. Here, we show that human ANT1 and ANT2, like yeast AAC2, do not function in isolation but have numerous binding partners including the respiratory supercomplex, Despite the differences in the organization of respiratory supercomplexes in yeast and mammals, wherein the latter additionally involves Complex I, the capacity of both AACs and ANTs to associate with it suggests an evolutionarily conserved interaction that has a functional importance.