Bacterial ancestry of the mitochondrial ATP exporter

Mitochondria originated through endosymbiosis of an Alphaproteobacterium within an Asgard archaeal host, with ATP export to the cytosol being a key driver for the organelle integration. The mitochondrial ATP/ADP carrier (AAC), a member of the SLC25 family, performs this critical function, whose evolutionary origin was not known due to the absence of any known prokaryotic homologues and was therefore termed a eukaryotic innovation. Here, using protein tertiary structure search combined with comprehensive sequence analyses, we identify conserved bacterial inner membrane transporters, CysZ and YihY, as putative homologues of mitochondrial AAC. CysZ and YihY are structurally similar to AAC, albeit with a circular permutation of one of the six transmembrane helices. Strikingly, we could identify the conserved MCF motif—a characteristic feature of the SLC25 family—in the bacterial sulfate transporter CysZ, suggesting a common ancestry. Together, our results identify a bacterial origin for the mitochondrial ATP exporter, thus resolving a long-standing question in mitochondrial evolution and a key step required for the emergence of eukaryotic cell complexity.