Decylubiquinone Increases Mitochondrial Function in Synaptosomes

Abstract

The effects of decylubiquinone, a ubiquinone analogue, on mitochondrial function and inhibition thresholds of the electron transport chain enzyme complexes in synaptosomes were investigated. Decylubiquinone increased complex I/III and complex II/III activities by 64 and 80%, respectively, and attenuated reductions in oxygen consumption at high concentrations of the complex III inhibitor myxothiazol. During inhibition of complex I, decylubiquinone attenuated reductions in synaptosomal oxygen respiration rates, as seen in the complex I inhibition threshold. Decylubiquinone increased the inhibition thresholds of complex I/III, complex II/III, and complex III over oxygen consumption in the nerve terminal by 25-50%, when myxothiazol was used to inhibit complex III. These results imply that decylubiquinone increases mitochondrial function in the nerve terminal during complex I or III inhibition. The potential benefits of decylubiquinone in diseases where complex I, I/III, II/III, or III activities are deficient are discussed.Numerous reports have suggested that ubiquinone (coenzyme Q 10 ) may have beneficial effects in neurodegenerative disorders (1-6). However, it is difficult to utilize ubiquinone in in vitro experiments because of its high level of hydrophobicity. Therefore, the beneficial effects of synthesized ubiquinone analogues, such as decylubiquinone (2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone), are under investigation. Decylubiquinone is an exogenous, hydrophobic quinone that has a 10-carbon side chain with a methyl group at the end and can travel into mitochondrial membranes unaided (7). Decylubiquinone accepts electrons from complex I and is reduced to decylubiquinol, which subsequently transfers electrons to complex III. Studies on the effect of decylubiquinone on the steadystate kinetics of complex I in bovine heart mitochondria showed that the binding of decylubiquinone induced a conformational change in the shape of the binding site, which allows the binding of a quinone with a long isoprenoid side chain (8). Decylubiquinone may be used favorably as an alternative to coenzyme Q 1 because the interaction of decylubiquinone with complex I is more similar to that between endogenous ubiquinone and complex I than between coenzyme Q 1 and complex I and because coenzyme Q 1 is not as efficient at activating complex I activity as decylubiquinone (9).In this study, the effects of decylubiquinone on the activities of a number of electron transport chain (ETC) 2 components, complexes I (EC 1.6.5.3), I/III (EC 1.6.99.3), II/III (EC 1.3.5.1 ϩ 1.10.2.2), and III (EC 1.10.2.2), in rat brain synaptosomes were examined. In addition, the effect of decylubiquinone on synaptosomal oxygen consumption, during titration with mitochondrial inhibitors, was investigated. Metabolic control analysis may be used to examine the spread of control among components in a system (10, 11), and the inhibition threshold is a useful parameter that describes mitochondrial function. The inhibition threshold is the level by which each co...

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