Brière Jean-Jacques, Schlemmer Dimitri, Chretien Domique, Rustin Pierre
Unités de Recherches sur les Handicaps Génétiques de l'Enfant (INSERM U393), Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75015 Paris, France.
Biochem Biophys Res Commun. 2004 Apr 16;316(4):1138-42. doi: 10.1016/j.bbrc.2004.03.002.
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.
醌衍生物是少数成功用作治疗线粒体疾病的治疗试剂的化合物。然而，它们的有益效果似乎取决于其侧链，侧链大概决定了它们与呼吸链的相互作用。通过亚线粒体组分对四种醌衍生物对NADH和琥珀酸竞争性氧化的影响进行了比较研究。在我们的实验条件下，疏水性较低的衍生物（甲萘醌、杜醌）对电子从NADH或琥珀酸流向氧气的影响较小，但很容易从分离的复合体I转移电子。添加琥珀酸后消除了后一种效应。疏水性更强的衍生物（艾地苯醌、癸基泛醌）刺激了琥珀酸的氧摄取。虽然艾地苯醌对NADH氧化有轻微抑制作用，但癸基泛醌则使其有所增加。结果，艾地苯醌强烈倾向于琥珀酸而非NADH氧化。因此，这项研究表明，醌类似物的任何治疗用途都应考虑它们对每个呼吸链脱氢酶的特定作用。
