Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Biochimica et biophysica acta, 2013-04, Vol.1831 (4), p.776-791

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Coenzyme Qn (ubiquinone or Qn) 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 Q6, 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 Q2, a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q6. 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 Q2, Q3, Q10, or demethoxy-Q3 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 Q6 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. [Display omitted] ► Yeast coq10 mutants respire very poorly yet have a normal content of coenzyme Q6. ► Expression of C. crescentus CC1736 START domain protein rescues the coq10 mutant. ► CC1736 binds Q3 or demethoxy-Q3, but doesn't bind 3-farnesyl-4-hydroxybenzoic acid. ► coq-10 mutants show decreased de novo Q synthesis and accumulate Q-intermediates. ► Coq10p facilitates Q biosynthesis and may deliver new Q to respiratory complexes.