Beyond its role in mitochondrial bioenergetics, Coenzyme Q (CoQ, ubiquinone) serves as a key membrane-embedded antioxidant throughout the cell. However, how CoQ is mobilized from its site of synthesis on the inner mitochondrial membrane to other sites of action remains a longstanding mystery. Here, using a combination ofSaccharomyces cerevisiae genetics, biochemical fractionation, and lipid profiling, we identify two highly conserved but poorly characterized mitochondrial proteins, Ypl109c (Cqd1) and Ylr253w (Cqd2), that reciprocally affect this process. Loss of Cqd1 skews cellular CoQ distribution away from mitochondria, resulting in markedly enhanced resistance to oxidative stress caused by exogenous polyunsaturated fatty acids, whereas loss of Cqd2 promotes the opposite effects.
Fig: Extramitochondrial CoQ combats oxidative stress: a Growth rate of wild type (WT) and ∆gpx1/2/3 yeast in synthetic complete media minus para-aminobenzoate (pABA−) containing 2% (w/v) glucose (mean ± SD, n = 3 independent samples) and the indicated additives. 4-HB, 4-hydroxybenzoate; 18:3, linolenic acid (PUFA). b Total CoQ from WT and ∆gpx1/2/3 yeast described in (a) (mean ± SD, n = 3 independent samples). c Rescue assay under the conditions described in (a) comparing the ability of decylubiquinone (DecylQ) and mitoquinone (MitoQ) to restore growth of ∆gpx1/2/3 yeast treated with 35 µM 18:3 (mean ± SD, n = 3 independent samples).
The activities of both proteins rely on their atypical kinase/ATPase domains, which they share with Coq8—an essential auxiliary protein for CoQ biosynthesis. Overall, our results reveal protein machinery central to CoQ trafficking in yeast and lend insights into the broader interplay between mitochondria and the rest of the cell.
Kemmerer, Z.A., Robinson, K.P., Schmitz, J.M. et al. UbiB proteins regulate cellular CoQ distribution in Saccharomyces cerevisiae. Nat Commun 12, 4769 (2021). https://doi.org/10.1038/s41467-021-25084-7