Discovery of EMRE in fungi resolves the true evolutionary history of the mitochondrial calcium uniporter

摘要: Mitochondrial calcium (mt-Ca2+) uptake is central for the regulation of numerous cellular processes in eukaryotes. This occurs through a highly selective Ca2+ uniporter located at inner mitochondrial membrane and driven by potential. While physiological role was extensively studied decades, its genetic identity only recently determined, with MCU, MICU1 EMRE constituting pore-forming regulatory subunits. Preliminary evolutionary analyses suggested an ancient eukaryotic origin mt-Ca2+ uptake, but also pinpointed inconsistent phylogenetic distributions MICU1, within fungi, where homologs MCU were present absence supposedly essential regulators, EMRE. Here, we perform most comprehensive phylogenomic analysis system trace evolution across 1,156 fully-sequenced In contrast to earlier assumptions find compelling evidence that previously identified animal fungal MCUs, targets several structural functional efforts, represent two distinct paralogous subfamilies originating from ancestral duplication. We further uncover complete animal-like complex chytrid including bona-fide orthologs first identification outside Holozoa (animals their unicellular relatives) strong coevolution indicates these three components formed core opisthokont uniporter. confirm this finding experimentally, showing combination either human or not fungal-specific can reconstitute vivo yeast Saccharomyces cerevisiae. Hence, here solve purported paradox: presence species devoid other no detectable uptake. Altogether, our study clarifies identifies new important comparative studies.