Ca-regulated mitochondrial carriers of ATP-Mg/Pi: Evolutionary insights in protozoans.

In addition to its uptake across the Ca uniporter, intracellular calcium signals can stimulate mitochondrial metabolism activating metabolite exchangers of the inner mitochondrial membrane belonging to the mitochondrial carrier family (SLC25). One of these Ca-regulated mitochondrial carriers (CaMCs) are the reversible ATP-Mg/Pi transporters, or SCaMCs, required for maintaining optimal adenine nucleotide (AdN) levels in the mitochondrial matrix representing an alternative transporter to the ADP/ATP translocases (AAC). This CaMC has a distinctive Calmodulin-like (CaM-like) domain fused to the carrier domain that makes its transport activity strictly dependent on cytosolic Ca signals. Here we investigate about its origin analysing its distribution and features in unicellular eukaryotes. Unexpectedly, we find two types of ATP-Mg/Pi carriers, the canonical ones and shortened variants lacking the CaM-like domain. Phylogenetic analysis shows that both SCaMC variants have a common origin, unrelated to AACs, suggesting in turn that recurrent losses of the regulatory module have occurred in the different phyla. They are excluding variants that show a more limited distribution and less conservation than AACs. Interestingly, these truncated variants of SCaMC are found almost exclusively in parasitic protists, such as apicomplexans, kinetoplastides or animal-patogenic oomycetes, and in green algae, suggesting that its lost could be related to certain life-styles. In addition, we find an intricate structural diversity in these variants that may be associated with their pathogenicity. The consequences on SCaMC functions of these new SCaMC-b variants are discussed.