Involvement of mitochondrial ferredoxin and para-aminobenzoic acid in yeast coenzyme Q biosynthesis.

Fabien Pierrel (1) , Olivier Hamelin (1) , Thierry Douki (2) , Sylvie Kieffer-Jaquinod (3) , Ulrich Mühlenhoff (4) , Mohammad Ozeir (1) , Roland Lill (5) , Marc Fontecave (1, 6)

1 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
2 LAN - Laboratoire Lésions des Acides Nucléiques
3 LEDyP - Laboratoire d'étude de la dynamique des protéomes
4 Fraunhofer IAIS - Fraunhofer Institute for Intelligent Analysis and Information Systems
5 Institut für Zytobiologie und Zytopathologie
6 Collège de France - Chaire Chimie des processus biologiques

Yeast ubiquinone or coenzyme Q(6) (Q(6)) is a redox active lipid that plays a crucial role in the mitochondrial electron transport chain. At least nine proteins (Coq1p-9p) participate in Q(6) biosynthesis from 4-hydroxybenzoate (4-HB). We now show that the mitochondrial ferredoxin Yah1p and the ferredoxin reductase Arh1p are required for Q(6) biosynthesis, probably for the first hydroxylation of the pathway. Conditional Gal-YAH1 and Gal-ARH1 mutants accumulate 3-hexaprenyl-4-hydroxyphenol and 3-hexaprenyl-4-aminophenol. Para-aminobenzoic acid (pABA) is shown to be the precursor of 3-hexaprenyl-4-aminophenol and to compete with 4-HB for the prenylation reaction catalyzed by Coq2p. Yeast cells convert U-((13)C)-pABA into (13)C ring-labeled Q(6), a result that identifies pABA as a new precursor of Q(6) and implies an additional NH(2)-to-OH conversion in Q(6) biosynthesis. Our study identifies pABA, Yah1p, and Arh1p as three actors in Q(6) biosynthesis.

Mots clés: ubiquinone; coenzyme Q; ferrédoxine; pABA

Domaines: Biochimie, Biologie Moléculaire

Fabien Pierrel, Olivier Hamelin, Thierry Douki, Sylvie Kieffer-Jaquinod, Ulrich Mühlenhoff, et al.. Involvement of mitochondrial ferredoxin and para-aminobenzoic acid in yeast coenzyme Q biosynthesis.: pABA is a precursor of yeast coenzyme Q. Chem Biol, 2010, 17 (5), pp.449-59. ⟨10.1016/j.chembiol.2010.03.014⟩. ⟨hal-00497916⟩