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Pittis, A.A.* ; Goh, V. ; Cebrian Serrano, A. ; Wettmarshausen, J. ; Perocchi, F. ; Gabaldón, T.*

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

Nat. Commun. 11, 4031 (2020)

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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. The mitochondrial calcium uptake system, crucial for cellular processes, evolved in ancient eukaryotes. Here, authors perform a phylogenomic analysis across 1,156 eukaryotes, and show that previously identified animal and fungal genes in this system originated from an ancestral duplication.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Micu1; Mcu; Protein; Homeostasis

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 11, Issue: 1, Pages: 4031

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)