The Endoplasmic Reticulum-Mitochondria Encounter Structure Complex Coordinates Coenzyme Q Biosynthesis

Abstract

Loss of the endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) complex that resides in contact sites between the yeast ER and mitochondria leads to impaired respiration; however, the reason for that is not clear. We find that in <i>ERMES</i> null mutants, there is an increase in the level of mRNAs encoding for biosynthetic enzymes of coenzyme Q₆ (CoQ₆), an essential electron carrier of the mitochondrial respiratory chain. We show that the mega complexes involved in CoQ₆ biosynthesis (CoQ synthomes) are destabilized in ERMES mutants. This, in turn, affects the level and distribution of CoQ₆ within the cell, resulting in reduced mitochondrial CoQ₆. We suggest that these outcomes contribute to the reduced respiration observed in ERMES mutants. Fluorescence microscopy experiments demonstrate close proximity between the CoQ synthome and ERMES, suggesting a spatial coordination. The involvement of the ER-mitochondria contact site in regulation of CoQ₆ biogenesis highlights an additional level of communication between these two organelles.