Journal of Lipid Research | |
Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function[S] | |
Marcus Gallagher-Jones1  Catherine F. Clarke2  Hope Ibarra3  Jason E. Gosschalk3  NguyenV.B. Pham3  Brendan R. Amer3  Michelle C. Bradley3  Crysten E. Blaby-Haas3  Hui S. Tsui3  Robert T. Clubb3  | |
[1] UCLA-Department of Energy Institute of Genomics and ProteomicsUniversity of California, Los Angeles, Los Angeles, CA 90095;Department of BiologyBrookhaven National Laboratory, Upton, NY 11973;Department of Chemistry and Biochemistry and Molecular Biology Institute,University of California, Los Angeles, Los Angeles, CA 90095; | |
关键词: antioxidants; lipids/chemistry; lipids/peroxidation; mass spectrometry; mitochondria; Saccharomyces cerevisiae; | |
DOI : | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown