Coenzyme q biosynthesis: coq6 is required for the c5-hydroxylation reaction and substrate analogs rescue coq6 deficiency.

Mohammad Ozeir (1) , Ulrich Mühlenhoff (2) , Holger Webert (2) , Roland Lill (2) , Marc Fontecave (1, 3) , Fabien Pierrel (1)

1 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
2 Institut für Zytobiologie und Zytopathologie
3 Collège de France - Chaire Chimie des processus biologiques

Coenzyme Q (Q), an essential component of eukaryotic cells, is synthesized by several enzymes from the precursor 4-hydroxybenzoic acid. Mutations in six of the Q biosynthesis genes cause diseases that can sometimes be ameliorated by oral Q supplementation. We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. In an unusual way, the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in vivo source of electrons for Coq6. We also show that hydroxylated analogs of 4-hydroxybenzoic acid, such as vanillic acid or 3,4-dihydroxybenzoic acid, restore Q biosynthesis and respiration in a Saccharomyces cerevisiae coq6 mutant. Our results demonstrate that appropriate analogs of 4-hydroxybenzoic acid can bypass a deficient Q biosynthetic enzyme and might be considered for the treatment of some primary Q deficiencies.

Domaines: Biochimie, Biologie Moléculaire

Mohammad Ozeir, Ulrich Mühlenhoff, Holger Webert, Roland Lill, Marc Fontecave, et al.. Coenzyme q biosynthesis: coq6 is required for the c5-hydroxylation reaction and substrate analogs rescue coq6 deficiency.. Chem Biol, 2011, 18 (9), pp.1134-42. ⟨10.1016/j.chembiol.2011.07.008⟩. ⟨hal-00630764⟩