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

This research investigates the evolutionary history of the mitochondrial calcium uniporter (MCU), a channel responsible for calcium influx into mitochondria. Previous studies revealed a paradox: fungal species possessed MCU homologs but lacked other uniporter components and mt-Ca²⁺ uptake. This study uses phylogenomic analysis across 1,156 eukaryotes to demonstrate that animal and fungal MCUs are distinct paralogs resulting from an ancestral duplication. EMRE orthologs were discovered outside Holozoa, and an animal-like uniporter was found in chytrid fungi, enabling mt-Ca²⁺ uptake when reconstituted in yeast. The study concludes that MCU, EMRE, and MICU formed the core of the ancestral uniporter, providing insights into comparative structural and functional studies.

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