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Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function.
J Lipid Res. 2019 07; 60(7):1293-1310.JL

Abstract

Coenzyme Q (CoQ or ubiquinone) 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 and 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 nonfermentable carbon source and sensitivity to oxidative stress induced by treatment with PUFAs. 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. Coexpression 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.

Authors+Show Affiliations

Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095. UCLA-Department of Energy Institute of Genomics and Proteomics University of California, Los Angeles, Los Angeles, CA 90095.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095.Department of Biology Brookhaven National Laboratory, Upton, NY 11973.Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095 cathy@chem.ucla.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

31048406

Citation

Tsui, Hui S., et al. "Human COQ10A and COQ10B Are Distinct Lipid-binding START Domain Proteins Required for Coenzyme Q Function." Journal of Lipid Research, vol. 60, no. 7, 2019, pp. 1293-1310.
Tsui HS, Pham NVB, Amer BR, et al. Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. J Lipid Res. 2019;60(7):1293-1310.
Tsui, H. S., Pham, N. V. B., Amer, B. R., Bradley, M. C., Gosschalk, J. E., Gallagher-Jones, M., Ibarra, H., Clubb, R. T., Blaby-Haas, C. E., & Clarke, C. F. (2019). Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. Journal of Lipid Research, 60(7), 1293-1310. https://doi.org/10.1194/jlr.M093534
Tsui HS, et al. Human COQ10A and COQ10B Are Distinct Lipid-binding START Domain Proteins Required for Coenzyme Q Function. J Lipid Res. 2019;60(7):1293-1310. PubMed PMID: 31048406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. AU - Tsui,Hui S, AU - Pham,Nguyen V B, AU - Amer,Brendan R, AU - Bradley,Michelle C, AU - Gosschalk,Jason E, AU - Gallagher-Jones,Marcus, AU - Ibarra,Hope, AU - Clubb,Robert T, AU - Blaby-Haas,Crysten E, AU - Clarke,Catherine F, Y1 - 2019/05/02/ PY - 2019/02/25/received PY - 2019/04/12/revised PY - 2019/5/3/pubmed PY - 2020/7/14/medline PY - 2019/5/4/entrez KW - Saccharomyces cerevisiae KW - antioxidants KW - lipids/chemistry KW - lipids/peroxidation KW - mass spectrometry KW - mitochondria KW - steroidogenic acute regulatory protein-related lipid transfer KW - ubiquinone SP - 1293 EP - 1310 JF - Journal of lipid research JO - J Lipid Res VL - 60 IS - 7 N2 - Coenzyme Q (CoQ or ubiquinone) 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 and 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 nonfermentable carbon source and sensitivity to oxidative stress induced by treatment with PUFAs. 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. Coexpression 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. SN - 1539-7262 UR - https://www.unboundmedicine.com/medline/citation/31048406/Human_COQ10A_and_COQ10B_are_distinct_lipid_binding_START_domain_proteins_required_for_coenzyme_Q_function_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2275(20)31061-0 DB - PRIME DP - Unbound Medicine ER -