Coq10, a mitochondrial coenzyme Q binding protein, is required for proper respiration in Schizosaccharomyces pombe

Abstract

It has been widely accepted that most coenzyme Q (CoQ) exists freely in the mitochondrial membrane as a CoQ pool. However, the recent identification of a mitochondrial CoQ‐binding protein, termed Coq10, in budding yeast has the potential to change our current view of CoQ status in membranes. Here, we studied the counterpart of budding yeast Coq10 (also termed Coq10) in fission yeast. Fission yeast coq10 null mutants exhibited a similar, but less severe, phenotype to CoQ‐deficient fission yeast, including the requirement for antioxidants for proper growth on minimal medium, increased sensitivity to H2O2, high levels of H2S production, and a deficiency in respiration. The coq10 null mutant produced nearly normal levels of CoQ10, suggesting that coq10 does not belong to the group of CoQ biosynthetic genes. To elucidate the role of Coq10, we expressed recombinant coq10 in Escherichia coli, and found that CoQ8 was present in purified recombinant Coq10. Mutational analysis of 13 conserved residues of Coq10 revealed that two hydrophobic amino acid residues, leucine 63 (L63) and tryptophan 104 (W104), play an important role in Coq10 binding to CoQ. An L63A/W104A double mutant of Coq10 exhibited lower CoQ‐binding activity than either of the single mutants, and was unable to complement the coq10 deletion in fission yeast. A human Coq10 ortholog was able to functionally compensate for the absence of coq10 in fission yeast, suggesting that Coq10 is important for proper respiration in a variety of organisms.

Identification of Coq11, a New Coenzyme Q Biosynthetic Protein in the CoQ-Synthome in Saccharomyces cerevisiae

“…Such fusion proteins, also known as Rosetta Stone proteins, are often indicative of a functional link between two proteins including a physical interaction or residency in the same pathway (73). Coq10 was shown to be required for efficient de novo Q biosynthesis (56), and several studies indicate that yeast Coq10 and orthologs bind Q or DMQ via a hydrophobic START domain (56,74,75), leading to the hypothesis that Coq10 acts a Q chaperone, necessary for delivery of Q to the CoQ-synthome for efficient de novo Q synthesis and respiration (56). The fusion of YLR290C with Coq10 strongly suggests a functional interaction of YLR290C with this Q-binding protein.…”

Glutamyl tRNA Synthetases and Glutamic Acid Induce Sexual Differentiation ofSchizosaccharomyces pombe

“…Especially, respiration is very important in the growth of fission yeast. 40,41) We also noticed that higher expression of the ers2 gene resulted in slow growth ( Fig. 2A, B), and decreased cell viability (Fig.…”

Menaquinone as Well as Ubiquinone as a Crucial Component in the Escherichia coli Respiratory Chain

“…Our preliminary experiments showed that an E. coli YfjG plays a function similar to that of Coq10 and allowed us to speculate that it interacts with UQ or MK to enhance the activity of electron transfer between dehydrogenase and ubiquinol oxidase. The alignment of YfjG orthologs in Gram-negative bacteria exhibited 11 highly conserved amino acid residues, which are partially overlapping with the conserved residues in Coq10 orthologs, some of which are involved in UQ binding (Cui & Kawamukai, 2009). A yfjG-disrupted mutant exhibited different properties in respiration activity of E. coli.…”

“…Recently, Barros et al (2005) speculated that Coq10 as a mitochondrial UQ-binding protein, which is not associated with succinate-and NADH-UQ reductase or the bc 1 complex in Saccharomyces cerevisiae, is involved in transport of UQ from its synthetic site to its functional site. Cui and Kawamukai (2009) reported that Coq10 binds to CoQ10 and is required for 11 proper respiration activity in Schizosaccharomyces pombe. These findings not only expand our knowledge of the regulation of UQ but also allow us to challenge the longstanding notion that UQ molecules are freely moving in the hydrophobic environment of membranes.…”