Characterization of SCaMC-3-Like/slc25a41 a novel calcium-independent mitochondrial ATP-Mg/Pi carrier
Résumé
The SCaMCs constitute a subfamily of mitochondrial carriers responsible of the ATP-Mg/Pi exchange with at least three paralogues in vertebrates. SCaMCs members are proteins with two functional domains the C-terminal transporter domain and the N-terminal one which harbours Ca2+-binding EF-hands and facing the intermembrane space. Here, we have characterised a shortened fourth paralog, SCaMC-3-Like (also named as Slc25a41), which lacks the Ca2+-binding N-extension. SCaMC-3-Like orthologues are found exclusively in mammals showing around 60% identity to the carboxyl-half of SCaMC-3, its closest paralog. In mammalian genomes, SCaMC-3 and SCaMC-3-Like genes are adjacent on the same chromosome, forming a head-to-tail tandem array and show identical exon-intron boundaries indicating that SCaMC-3-Like could have arisen from a SCaMC-3 ancestor by a partial duplication event which occurred prior to mammalian radiation. Expression and functional data suggest that following the duplication event, SCaMC-3-Like has acquired more restrictive functions. Unlike the broadly expressed longer SCaMCs, mouse SCaMC-3-Like shows a limited expression pattern; it is preferentially expressed in testis and, at lower levels, in brain. SCaMC-3-Like transport activity was studied in yeast deficient in Sal1p, the Ca2+-dependent mitochondrial ATP-Mg/Pi carrier, co-expressing SCaMC-3-Like and mitochondrial-targeted luciferase, and it was found to perform ATP-Mg/Pi exchange, as Sal1p or other ATP-Mg/Pi carriers. However, metabolite transport through SCaMC-3-Like is Ca2+-independent, representing a novel mechanism involved in adenine nucleotide transport across the inner mitochondrial membrane different to ADP/ATP translocases or long SCaMC paralogues.
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