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

Alexandros A. Pittis, Valerie Goh, Alberto Cebrian-Serrano, Jennifer Wettmarshausen, Fabiana Perocchi, Toni Gabaldón

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

16 Zitate (Scopus)

Abstract

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.

OriginalspracheEnglisch
Aufsatznummer4031
FachzeitschriftNature Communications
Jahrgang11
Ausgabenummer1
DOIs
PublikationsstatusVeröffentlicht - 1 Dez. 2020
Extern publiziertJa

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