A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae

作者：Allan Christopher M; Hill Shauna; Morvaridi Susan; Saiki Ryoichi; Johnson Jarrett S; Liau Wei Siang; Hirano Kathleen; Kawashima Tadashi; Ji Ziming; Loo Joseph A; Shepherd Jennifer N; Clarke Catherine F^*

来源：Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2013, 1831(4): 776-791.

DOI：10.1016/j.bbalip.2012.12.007

• Ubiquinone
• Yeast mitochondria
• Lipid binding
• Steroidogenic acute regulatory protein
• Respiratory electron transport
• Lipid autoxidation

Coenzyme Q(n) (ubiquinone or Q(n)) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail of n isoprene units. Saccharomyces cerevisiae coq1-coq9 mutants have defects in Q biosynthesis, lack Q(6), are respiratory defective, and sensitive to stress imposed by polyunsaturated fatty acids. The hallmark phenotype of the Q-less yeast coq mutants is that respiration in isolated mitochondria can be rescued by the addition of Q(2), a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q(6). Structure determination of the Caulobacter crescentus Coq10 homolog (CC1736) revealed a steroidogenic acute regulatory protein-related lipid transfer (START) domain, a hydrophobic tunnel known to bind specific lipids in other START domain family members. Here we show that purified CC1736 binds Q(2), Q(3), Q(10), or demethoxy-Q(3) in an equimolar ratio, but fails to bind 3-farnesyl-4-hydroxybenzoic acid, a farnesylated analog of an early Q-intermediate. Over-expression of C crescentus CC1736 or COQ8 restores respiratory electron transport and antioxidant function of Q(6) in the yeast coq10 null mutant. Studies with stable isotope ring precursors of Q reveal that early Q-biosynthetic intermediates accumulate in the coq10 mutant and de novo Q-biosynthesis is less efficient than in the wild-type yeast or rescued coq10 mutant. The results suggest that the Coq10 polypeptide:Q (protein:ligand) complex may serve essential functions in facilitating de novo Q biosynthesis and in delivering newly synthesized Q to one or more complexes of the respiratory electron transport chain.

• 出版日期2013-4