Studies of quinone biosynthesis and connection to metabolism

Heads Dr Fabien Pierrel and Dr Ludovic Pelosi

Ubiquinone, also named coenzyme Q (Q), is a redox-active lipid essential for electron and proton transport in a multitude of respiratory chains which sustain energy production in a wide range of organisms ranging from bacteria to mammals. Q is also an antioxidant in cellular membranes and serves other important functions as a cofactor of uncoupling proteins, a modulator of the mitochondrial transition pore or a membrane stabilizer in bacteria. Given the physiological importance of Q, it is not surprising that a deficiency in Q leads to strong phenotypes. In humans, primary Q deficiencies caused by mutations in genes coding for Q biosynthetic proteins result in severe clinically heterogeneous diseases while in microorganisms, Q deficiency profoundly affects metabolism. The biosynthesis of Q is a multi-step biochemical pathway requiring a dozen of genes, most of them conserved from bacteria to man. Even though active research has been conducted on Q for a long time, important questions remain regarding:

  • The identity and mechanism of proteins catalyzing some reactions of Q biosynthesis.
  • The regulation and cellular organization of Q biosynthesis.
  • The contribution of Q and the other bacterial quinones to metabolism in varying environmental conditions.

We are trying to address these questions by using genetic and biochemical approaches on several organisms. The yeast Saccharomyces cerevisiae is an excellent genetic model to study some aspects of Q biosynthesis and the results obtained often contribute to a better understanding of Q metabolism in humans. We also study the model bacterium Escherichia coli in order to i) understand the regulation and biochemical details of Q biosynthesis and ii) study how the evolution of the quinone pool (Q + menaquinones) impacts on the metabolism and fitness. In the light of our recent collaborative discovery that Q is important for the pathogenicity of Salmonella typhimurium, we have recently started a project with on the study of Q biosynthetic pathways in pathogens, especially on pathogenic bacteria Francisella tularensis.

Coenzyme Q / ubiquinone biosynthesis chemical pathway in E. coli and in S. cerevisiae.

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3D-structure of UbiI, a new protein in E. coli coenzyme Q biosynthesis involved in aerobic C5-hydroxylation.

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Recent published articles:

Coq6 is Responsible for the C4-Deamination Reaction in Coenzyme Q Biosynthesis in Saccharomyces cerevisiae, Ozeir M., Pelosi L., Ismail A., Mellot-Draznieks C., Fontecave M., Pierrel F. J Biol Chem (2015) 290:24140-51

Demethylmenaquinol is a substrate of Escherichia coli nitrate reductase A (NarGHI) and forms a stable semiquinone intermediate at the NarGHI quinol oxidation site. Rendon J., Pilet E., Fahs Z., Seduk F., Sylvi L., Hajj Chehade M., Pierrel F., Guigliarelli B., Magalon A., Grimaldi S. Biochim Biophys Acta (2015) 1847:739-47

Three conserved histidyl residues contribute to mitochondrial iron transport through mitoferrins. Brazzolotto X., Pierrel F., Pelosi L. Biochemical Journal (2014) 460:79-89

Biosynthesis and physiology of coenzyme Q in bacteria. Aussel L., Pierrel F., Loiseau L., Lombard M., Fontecave M., Barras F. Biochim Biophys Acta (2014) 1837:1004-11

Effect of vanillic acid on COQ6 mutants identified in patients with coenzyme Q10 deficiency. Doimo M., Trevisson E., Airik R., Bergdoll M., Santos-Ocaña C., Hildebrandt F., Navas P., Pierrel F., Salviati L. Biochim Biophys Acta (2014) 1842: 1-6

Coenzyme Q biosynthesis in Escherichia coli and Salmonella typhimurium: ubiJ, a new gene required for aerobic growth and proliferation in macrophage. Aussel L., Loiseau L., Hajj Chehade M., Pocachard B., Fontecave M., Pierrel F., Barras F. J Bact (2014) 196: 70-9

Laboratoire TIMC-IMAG, Domaine de la Merci, 38706 La Tronche Cedex

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