Vps1 and select autophagic machinery are required for coenzyme Q uptake and trafficking to mitochondria.

Coenzyme Q (CoQ) is an important lipid found in nearly all cellular membranes in eukaryotes. Biosynthesis of CoQ occurs within mitochondria, where it functions as an electron carrier in oxidative phosphorylation and participates in key metabolic pathways. In both mitochondrial and non-mitochondrial membranes, the hydroquinone form of CoQ (CoQH2) also functions as a radical-scavenging antioxidant and participates in other processes required for cell maintenance and survival. Individuals with CoQ deficiency may benefit from high-dose CoQ supplementation; however, its bioavailability is limited, and treatment responses can vary. Here, we sought to gain mechanistic insight into how exogenous CoQ is trafficked to mitochondria. We used the yeast model system Saccharomyces cerevisiae, that produce CoQ6 with a polyisoprenyl tail containing six isoprene units. A CoQ6-deficient (coq2Δ) yeast mutant is used to investigate genes and corresponding pathways required for the cellular uptake and trafficking of exogenous CoQ6 to mitochondrial respiratory complexes. Specifically, we identify essential residues in the dynamin-like protein Vps1 that are required for CoQ6 trafficking and show that yeast vps1 mutants with known defects in autophagy are incapable of trafficking exogenously supplemented CoQ6 to mitochondria. Importantly, we identify a non-canonical role for several autophagic proteins in CoQ6 trafficking. Taken together, our data suggest that uptake of exogenous CoQ6 and its delivery to the mitochondria relies on a novel, specialized lipid trafficking pathway comprised of select autophagic and endosomal membrane trafficking proteins, and the lytic compartment which serves as a transport hub.