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

Calcium (Ca2+) influx into mitochondria occurs through a Ca2+-selective uniporter channel, which regulates essential cellular processes in eukaryotic organisms. Previous evolutionary analyses of its pore-forming subunits MCU and EMRE, and gatekeeper MICU1, pinpointed an evolutionary paradox: the pre...

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Bibliographic Details
Authors: Pittis, Alexandros A., Goh, Valerie, Cebrian Serrano, Alberto, Wettmarshausen, Jennifer, Perocchi, Fabiana, Gabaldón, Toni
Format: article
Publication Date:2020
Country:España
Institution:Universitat Politècnica de Catalunya (UPC)
Repository:UPCommons. Portal del coneixement obert de la UPC
Language:English
OAI Identifier:oai:upcommons.upc.edu:2117/378471
Online Access:https://hdl.handle.net/2117/378471
https://dx.doi.org/10.1038/s41467-020-17705-4
Access Level:Open access
Keyword:Candida
Phylogenetics
Eukaryote
Mitochondria
Phylogenomics
Simulació per ordinador
Genètica
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
Description
Summary:Calcium (Ca2+) influx into mitochondria occurs through a Ca2+-selective uniporter channel, which regulates essential cellular processes in eukaryotic organisms. Previous evolutionary analyses of its pore-forming subunits MCU and EMRE, and gatekeeper MICU1, pinpointed an evolutionary paradox: the presence of MCU homologs in fungal species devoid of any other uniporter components and of mt-Ca2+ uptake. Here, we trace the mt-Ca2+ uniporter evolution across 1,156 fully-sequenced eukaryotes and show that animal and fungal MCUs represent two distinct paralogous subfamilies originating from an ancestral duplication. Accordingly, we find EMRE orthologs outside Holoza and uncover the existence of an animal-like uniporter within chytrid fungi, which enables mt-Ca2+ uptake when reconstituted in vivo in the yeast Saccharomyces cerevisiae. Our study represents the most comprehensive phylogenomic analysis of the mt-Ca2+ uptake system and demonstrates that MCU, EMRE, and MICU formed the core of the ancestral opisthokont uniporter, with major implications for comparative structural and functional studies.

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