Discovery of EMRE in fungi resolves the true evolutionary history of the mitochondrial calcium uniporter
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Abstract
Calcium (Ca 2+ ) influx into mitochondria occurs through a Ca 2+ -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-Ca 2+ uptake. Here, we trace the mt-Ca 2+ 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-Ca 2+ uptake when reconstituted in vivo in the yeast Saccharomyces cerevisiae . Our study represents the most comprehensive phylogenomic analysis of the mt-Ca 2+ 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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Under ER stress, Ca2+ in the ER may leak into the cytoplasm, potentially increasing Ca2+ availability within mitochondria.
“Under ER stress, Ca2+ in the ER may leak into the cytoplasm, potentially resulting in an increase in the availability of Ca2+ within the mitochondria35,36.”
From Impairing the interaction between Erg11 and cytochrome P450 reductase Ncp1 enhances azoles’ antifungal activities (2025) · cites this paper as [35]
The Introduction says mitochondria rapidly take up and buffer cytosolic Ca2+, supporting the proposed mitochondrial uptake step. It does not address ER stress or Ca2+ leaking from the ER into the cytoplasm; searches for those terms found no relevant passage. No page number was provided in our copy. (LLM, conf=0.78)
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- Authors
- Pittis, A. A., Goh, V., Cebrian-Serrano, A., Wettmarshausen, J., Perocchi, F., & Gabaldón, T.
- Affiliations
- University of British Columbia (CA)
- Helmholtz Munich (DE)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Perocchi, Fabiana
- Gabaldón, Toni
- Venue
- Nature Communications
- Published
- 2020-08-12
- Volume
- 11
- Issue
- 1
- Pages
- 4031-4031
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7423614
- OpenAlex
- W3048365042
- Cited by
- 29
- References
- 48
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 3
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion, cc-by)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- UPCommons institutional repository (Universitat Politècnica de Catalunya) (submittedVersion, cc-by)
- Funders
- Vallee Foundation
- Centres de Recerca de Catalunya
- European Commission (390857198, HORIZON2020, ERC-2016-724173)
- Generalitat de Catalunya
- Agència de Gestió d'Ajuts Universitaris i de Recerca (SGR857)
- Instituto de Salud Carlos III
- European Regional Development Fund (BFU2015-67107)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- mitochondrial calcium uniporter, EmrE, MCU, MICU1, mitochondrial calcium uptake, fungal evolution, chytrid fungus, opisthokonts, gene duplication, phylogenomics
- MeSH terms
- Amino Acid Sequence, Calcium, Fungal Proteins, HeLa Cells, Humans, Chytridiomycota, Phylogeny, Species Specificity, Calcium Channels, Likelihood Functions, Evolution, Molecular
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