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Title: Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function

Abstract

We report that coenzyme Q (ubiquinone or CoQ) serves as an essential redox-active lipid in respiratory electron and proton transport during cellular energy metabolism. CoQ also functions as a membrane-localized antioxidant protecting cells against lipid peroxidation. CoQ deficiency is associated with multiple human diseases; CoQ10 supplementation in particular has noted cardioprotective benefits. In Saccharomyces cerevisiae, Coq10, a putative START domain protein, is believed to chaperone CoQ to sites where it functions. Yeast coq10 deletion mutants (coq10Δ) synthesize CoQ inefficiently during log phase growth, are respiratory defective and sensitive to oxidative stress. Humans have two orthologs of yeast COQ10, COQ10A and COQ10B. Here, we tested the human co-orthologs for their ability to rescue the yeast mutant. We showed that expression of either human ortholog, COQ10A or COQ10B, rescues yeast coq10Δ mutant phenotypes, restoring the function of respiratory-dependent growth on a non-fermentable carbon source and sensitivity to oxidative stress induced by treatment with polyunsaturated fatty acids. These effects indicate a strong functional conservation of Coq10 across different organisms. However, neither COQ10A nor COQ10B restored CoQ biosynthesis when expressed in the yeast coq10Δ mutant. The involvement of yeast Coq10 in CoQ biosynthesis may rely on its interactions with another protein, possibly Coq11, whichmore » is not found in humans. Lastly, co-expression analyses of yeast COQ10, and human COQ10A and COQ10B provide additional insights to functions of these START domain proteins, and their potential roles in other biologic pathways.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]; ORCiD logo [2];  [1]
  1. Univ. of California, Los Angeles, CA (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States)
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1556881
Report Number(s):
BNL-211981-2019-JAAM
Journal ID: ISSN 0022-2275
Grant/Contract Number:  
SC0012704
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Lipid Research
Additional Journal Information:
Journal Volume: 60; Journal Issue: 7; Journal ID: ISSN 0022-2275
Publisher:
American Society for Biochemistry and Molecular Biology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Antioxidants; Lipids; Chemistry; Peroxidation; Mass spectrometry; Mitochondria

Citation Formats

Tsui, Hui S., Pham, Nguyen V. B., Amer, Brendan R., Bradley, Michelle C., Gosschalk, Jason E., Gallagher-Jones, Marcus, Ibarra, Hope, Clubb, Robert T., Blaby-Haas, Crysten E., and Clarke, Catherine F. Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. United States: N. p., 2019. Web. doi:10.1194/jlr.M093534.
Tsui, Hui S., Pham, Nguyen V. B., Amer, Brendan R., Bradley, Michelle C., Gosschalk, Jason E., Gallagher-Jones, Marcus, Ibarra, Hope, Clubb, Robert T., Blaby-Haas, Crysten E., & Clarke, Catherine F. Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. United States. https://doi.org/10.1194/jlr.M093534
Tsui, Hui S., Pham, Nguyen V. B., Amer, Brendan R., Bradley, Michelle C., Gosschalk, Jason E., Gallagher-Jones, Marcus, Ibarra, Hope, Clubb, Robert T., Blaby-Haas, Crysten E., and Clarke, Catherine F. Thu . "Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function". United States. https://doi.org/10.1194/jlr.M093534. https://www.osti.gov/servlets/purl/1556881.
@article{osti_1556881,
title = {Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function},
author = {Tsui, Hui S. and Pham, Nguyen V. B. and Amer, Brendan R. and Bradley, Michelle C. and Gosschalk, Jason E. and Gallagher-Jones, Marcus and Ibarra, Hope and Clubb, Robert T. and Blaby-Haas, Crysten E. and Clarke, Catherine F.},
abstractNote = {We report that coenzyme Q (ubiquinone or CoQ) serves as an essential redox-active lipid in respiratory electron and proton transport during cellular energy metabolism. CoQ also functions as a membrane-localized antioxidant protecting cells against lipid peroxidation. CoQ deficiency is associated with multiple human diseases; CoQ10 supplementation in particular has noted cardioprotective benefits. In Saccharomyces cerevisiae, Coq10, a putative START domain protein, is believed to chaperone CoQ to sites where it functions. Yeast coq10 deletion mutants (coq10Δ) synthesize CoQ inefficiently during log phase growth, are respiratory defective and sensitive to oxidative stress. Humans have two orthologs of yeast COQ10, COQ10A and COQ10B. Here, we tested the human co-orthologs for their ability to rescue the yeast mutant. We showed that expression of either human ortholog, COQ10A or COQ10B, rescues yeast coq10Δ mutant phenotypes, restoring the function of respiratory-dependent growth on a non-fermentable carbon source and sensitivity to oxidative stress induced by treatment with polyunsaturated fatty acids. These effects indicate a strong functional conservation of Coq10 across different organisms. However, neither COQ10A nor COQ10B restored CoQ biosynthesis when expressed in the yeast coq10Δ mutant. The involvement of yeast Coq10 in CoQ biosynthesis may rely on its interactions with another protein, possibly Coq11, which is not found in humans. Lastly, co-expression analyses of yeast COQ10, and human COQ10A and COQ10B provide additional insights to functions of these START domain proteins, and their potential roles in other biologic pathways.},
doi = {10.1194/jlr.M093534},
url = {https://www.osti.gov/biblio/1556881}, journal = {Journal of Lipid Research},
issn = {0022-2275},
number = 7,
volume = 60,
place = {United States},
year = {2019},
month = {5}
}

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