Jun 6, 2014

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

BioRxiv : the Preprint Server for Biology
Alyssa C FrazeeToni Gabaldon

Abstract

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 the inner mitochondrial membrane and driven by the membrane potential. While the physiological role of the uniporter was extensively studied for decades, its genetic identity was only recently determined, with MCU, MICU1 and EMRE constituting pore-forming and regulatory subunits. Preliminary evolutionary analyses suggested an ancient eukaryotic origin of mt-Ca2+ uptake, but also pinpointed inconsistent phylogenetic distributions of MCU, MICU1, and EMRE within fungi, where homologs of MCU were present in the absence of the supposedly essential regulators, MICU1 and EMRE. Here, we perform the most comprehensive phylogenomic analysis of the mt-Ca2+ uptake system and trace its evolution across 1,156 fully-sequenced eukaryotes. In contrast to earlier assumptions we find compelling evidence that previously identified animal and fungal MCUs, the targets of several structural and functional efforts, represent two distinct paralogous subfamilies originating from an ancestral duplication. We further uncover a complete animal-like uniporter complex within chytri...Continue Reading

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