Endogenous synthesis of coenzyme Q in eukaryotes

Abstract

Coenzyme Q (Q) functions in the mitochondrial respiratory chain and serves as a lipophilic antioxidant. There is increasing interest in the use of Q as a nutritional supplement. Although, the physiological significance of Q is extensively investigated in eukaryotes, ranging from yeast to human, the eukaryotic Q biosynthesis pathway is best characterized in the budding yeast Saccharomyces cerevisiae. At least ten genes (COQ1-COQ10) have been shown to be required for Q biosynthesis and function in respiration. This review highlights recent knowledge about the endogenous synthesis of Q in eukaryotes, with emphasis on S. cerevisiae as a model system.

Fig. 1. Proposed Q biosynthetic pathway in eukaryotes

The length of the polyisoprenoid chain of Q, designated by n, varies depending on the species; n = 6 in S. cerevisiae, 9 in C. elegans, and 10 in H. sapiens. In S. cerevisiae, there are nine identified Coq proteins necessary for the synthesis of QH₂ from dimethylallyl diphosphate and isopentenyl diphosphate precursors. The enzymatic functions of Coq4, Coq6, Coq8 and Coq9 polypeptides have yet to be characterized. Molecular oxygen and AdoMet are proposed donors for the hydroxy and methyl group, respectively (Olson and Rudney, 1983). CLK-1 is the C. elegans Coq7 homologue.

Fig. 2. A model of the mitochondrial Q biosynthetic protein complex in S. cerevisiae

The putative complex contains six Coq polypeptides which are peripherally associated with the inner mitochondrial membrane (dark grey octagons) and a spanning integral membrane Coq protein (hatched rectangle). Proposed lipid components of the multi-subunit complexes include DMQ₆ (black hexagon) and the final product Q₆ (white hexagon). The stoichiometry of the components has yet to be determined.