UbiB proteins regulate cellular CoQ distribution in Saccharomyces cerevisiae

Zachary A. Kemmerer, Kyle P. Robinson, Jonathan M. Schmitz, Mateusz Manicki, Brett R. Paulson, Adam Jochem, Paul D. Hutchins, Joshua J. Coon and David J. Pagliarini ()
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Zachary A. Kemmerer: Morgridge Institute for Research
Kyle P. Robinson: Morgridge Institute for Research
Jonathan M. Schmitz: Morgridge Institute for Research
Mateusz Manicki: Washington University School of Medicine
Brett R. Paulson: University of Wisconsin-Madison
Adam Jochem: Morgridge Institute for Research
Paul D. Hutchins: University of Wisconsin-Madison
Joshua J. Coon: University of Wisconsin-Madison
David J. Pagliarini: Morgridge Institute for Research

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract 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 of Saccharomyces 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. 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25084-7

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DOI: 10.1038/s41467-021-25084-7

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