Involvement of mitochondrial ferredoxin and para-aminobenzoic acid in yeast coenzyme Q biosynthesis.
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.
Pierrel
Fabien
F
Laboratoire de Chimie et Biologie des Métaux, UMR5249 CNRS-CEA-UJF, CEA Grenoble, F-38054 Grenoble Cedex 9, France. fabien.pierrel@cea.fr
Hamelin
Olivier
O
Douki
Thierry
T
Kieffer-Jaquinod
Sylvie
S
Mühlenhoff
Ulrich
U
Ozeir
Mohammad
M
Lill
Roland
R
Fontecave
Marc
M
D010129:4-Aminobenzoic Acid / Q000378:metabolism*; D000325:Adrenodoxin / Q000378:metabolism*; D000627:Aminophenols / Q000378:metabolism; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D010084:Oxidation-Reduction; D010226:Parabens / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014451:Ubiquinone / Q000096:biosynthesis*
D000627:Aminophenols; D008565:Membrane Proteins; D010226:Parabens; D029701:Saccharomyces cerevisiae Proteins; C120375:YAH1 protein, S cerevisiae; D000325:Adrenodoxin; D014451:Ubiquinone; C492747:Arh1 protein, S cerevisiae; D005287:Ferredoxin-NADP Reductase; C038193:4-hydroxybenzoic acid; C026729:4-aminophenol; D010129:4-Aminobenzoic Acid