UC San Diego

Mitochondrial calcium uniporters, MCUs, are oligomeric channel proteins found in the mitochondrial inner membrane. MCUs have two well conserved transmembrane helices (TMSs), connected by a linker which is also found in bacterial MCUs. These proteins are shown to be homologous to prokaryotic Mg²⁺ transporters, AtpI and AtpZ , based on comparison scores of up to 14.5 S.D. A phylogenetic tree containing these proteins, in addition to eukaryotic AtpI homologues, showed that the AtpI and AtpZ proteins cluster separately from each other and the MCUs, while the eukaryotic AtpIs cluster in between these two major groups. The MCUs and AtpZs share the same 2 TMS topology, but the AtpIs have 4 TMSs. Binary alignments, comparison scores and motif analyses showed that TMSs 1 and 2 align with TMSs 3 and 4 of the AtpIs, suggesting that the 4 TMS AtpI proteins arose via an intragenic duplication event. These findings establish an evolutionary link interconnecting eukaryotic and prokaryotic Ca²⁺ and Mg²⁺ transporters and reveal their structural relationships