Antioxidant function of coenzyme Q and the role of the ABC1/COQ8 gene in coenzyme Q biosynthesis in the yeast Saccharomyces cerevisiae

Coenzyme Q (ubiquinone or Q is most commonly known as an essential component of the mitochondrial respiratory chain, ferrying electrons from complexes I and II to complex III. However, by virtue of its ability to redox cycle, it has been proposed that Q may also function as an antioxidant. Much in vitro evidence has shown that it can function in this capacity. However, in vivo evidence has been lacking.; In the yeast Saccharomyces cerevisiae, the COQ1-COQ8 genes have been found to be essential for Q biosynthesis. coq mutants are unable to synthesize Q and are respiratory deficient. Utilizing this yeast system, we set up studies to investigate the role of Q as an antioxidant. The findings indicate that Q-deficient yeast mutants are more susceptible to oxidative stress through exposure to polyunsaturated fatty acids. These findings suggested that Q does have a functional role as a lipid soluble antioxidant in vivo in the yeast S. cerevisiae.; In S. cerevisiae, studies of Q biosynthesis revolve around the characterization of the COQ1-COQ8 genes and their corresponding gene products. Our study of the COQ8 gene revealed that it is ABC1, previously independently isolated as a multicopy suppressor of a cytochrome b mRNA translation defect. Previous characterization of abc1 mutants suggested that the mitochondrial respiratory complexes were thermosensitive and functioned inefficiently, and interestingly, levels of Q were reported to be similar to wild-type cells. These initial observations led to the suggestion that the Abc1 polypeptide may act as a chaperone-like protein essential for the proper conformation and functioning of the bc₁ and its neighboring complexes.; The independent isolation of COQ8/ABC1 as a multicopy suppressor and its suggested function as a chaperone was intriguing. However, the reported finding that abc1 mutants possessed near wild-type Q levels contradicted our observation that coq8 mutants were Q-deficient. Our further investigation established that coq8/abc1 mutants are non-respiring and Q-deficient, and that the sole critical defect leading to a lack of respiration is a lack of Q. The findings also indicate that the previously observed thermosensitivity and inefficient functioning of the respiratory complexes due to deletion of the COQ8/ABC1 gene stems from a general deficiency in respiration, rather than a specific lack of Q or dysfunction of the COQ/ABC1 gene product.