Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxylation reaction and substrate analogs rescue Coq6 deficiency

Chem Biol. 2011 Sep 23;18(9):1134-42. doi: 10.1016/j.chembiol.2011.07.008.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenodoxin / metabolism
  • Chromatography, High Pressure Liquid
  • Ferredoxin-NADP Reductase / metabolism
  • Hydroxybenzoates / chemistry
  • Hydroxybenzoates / pharmacology
  • Hydroxylation
  • Membrane Proteins / metabolism
  • Mutation
  • Parabens / chemistry
  • Parabens / pharmacology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Ubiquinone / biosynthesis*
  • Ubiquinone / deficiency
  • Ubiquinone / genetics
  • Ubiquinone / metabolism
  • Vanillic Acid / chemistry
  • Vanillic Acid / pharmacology


  • Hydroxybenzoates
  • Membrane Proteins
  • Parabens
  • Saccharomyces cerevisiae Proteins
  • YAH1 protein, S cerevisiae
  • ubiquinone 6
  • Adrenodoxin
  • Ubiquinone
  • protocatechuic acid
  • Arh1 protein, S cerevisiae
  • Ferredoxin-NADP Reductase
  • Vanillic Acid
  • 4-hydroxybenzoic acid