title: Quinone analogues regulate mitochondrial substrate competitive oxidation.
abstract: Quinone derivatives are among the rare compounds successfully used as therapeutic reagents to fight mitochondrial diseases. However, their beneficial effect appears to depend on their side chain which presumably governs their interaction with the respiratory chain. The effect of four quinone derivatives was comparatively studied on NADH- and succinate-competitive oxidation by a sub-mitochondrial fraction. Under our experimental conditions, the less hydrophobic derivatives (menadione, duroquinone) poorly affected electron flow from either NADH or succinate to oxygen, yet readily diverting electrons from isolated complex I. This latter effect was abolished by succinate addition. More hydrophobic derivatives (idebenone, decylubiquinone) stimulated oxygen uptake from succinate. But while NADH oxidation was slightly inhibited by idebenone, it was somewhat increased by decylubiquinone. As a result, idebenone strongly favoured succinate over NADH oxidation. This study therefore suggests that any therapeutic use of quinone analogues should take into account their specific effect on each respiratory chain dehydrogenase.
authors.affiliation: Unités de Recherches sur les Handicaps Génétiques de l'Enfant (INSERM U393), Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75015 Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Brière
authors.forename: Dimitri
authors.initials: D
authors.lastname: Schlemmer
authors.forename: Domique
authors.initials: D
authors.lastname: Chretien
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D001667:Binding, Competitive / Q000502:physiology; D019069:Cell Respiration / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology*; D013379:Substrate Specificity; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D024483:Vitamin K 3 / Q000494:pharmacology
chemical_list: D016227:Benzoquinones; D011809:Quinones; D009243:NAD; D014451:Ubiquinone; C060262:2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone; D024483:Vitamin K 3; C036619:idebenone; D010100:Oxygen; C034257:duroquinone