Unidirectional effect of lauryl sulfate on the reversible NADH:ubiquinone oxidoreductase (Complex I)

Grivennikova, Vera G.; Ushakova, Alexandra V.; Cecchini, Gary; Vinogradov, Andrei D.

doi:10.1016/s0014-5793(03)00765-8

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…It is therefore clear that the inhibitory effect of 1 on the reverse electron transfer is significantly weaker than that on the forward electron transfer, indicating a direction-specific effect. More experiments are needed to determine whether this phenomenon is associated with the possibility that different electron transfer pathways operate in the two reactions (37).…”

Section: Resultsmentioning

confidence: 99%

“…On the basis of Lineweaver-Burk plots of the kinetic data on NADH-Q 1 oxidoreductase activity, we previously suggested that ∆lac-acetogenins inhibit complex I in a competitive manner against Q 1 (23). However, this idea has to be revised since the problem inherent to the studies employing Michaelis-Menten-type kinetics (6,31,32,37,52) is that the physicochemical properties of the ubiquinones, the inhibitors, and the membrane-bound enzyme as well as the complexity of underlying catalytic mechanism make interpretation of the kinetic data difficult and ambiguous. In particular, hydrophobic ubiquinones and inhibitors remarkably accumulate in the hydrophobic lipid phase of the inner mitochondrial membrane, making the actual concentrations at the reaction sites difficult to determine.…”

Section: Discussionmentioning

confidence: 99%

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Mode of Inhibitory Action of Δlac-Acetogenins, a New Class of Inhibitors of Bovine Heart Mitochondrial Complex I

et al. 2006

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We have revealed that Deltalac-acetogenins, a new class of inhibitors of bovine heart mitochondrial complex I (NADH-ubiquinone oxidoreductase), act differently from ordinary inhibitors such as rotenone and piericidin A [Ichimaru et al. (2005) Biochemistry 44, 816-825]. Since a detailed study of these unique inhibitors might provide new insight into the terminal electron transfer step of the enzyme, we further characterized their inhibitory action using the most potent Deltalac-acetogenin derivative (compound 1). Unlike ordinary complex I inhibitors, 1 had a dose-response curve for inhibition of the reduction of exogenous short-chain ubiquinones that was difficult to explain with a simple bimolecular association model. The inhibitory effect of 1 on ubiquinol-NAD(+) oxidoreductase activity (reverse electron transfer) was much weaker than that on NADH oxidase activity (forward electron transfer), indicating a direction-specific effect. These results suggest that the binding site of 1 is not identical to that of ubiquinone and the binding of 1 to the enzyme secondarily (or indirectly) disturbs the redox reaction of ubiquinone. Using endogenous and exogenous ubiquinone as an electron acceptor of complex I, we investigated the effect of 1 in combination with different ordinary inhibitors on the superoxide production from the enzyme. The results indicated that the level of superoxide production induced by 1 is significantly lower than that induced by ordinary inhibitors probably because of fewer electron leaks from the ubisemiquinone radical to molecular oxygen and that the site of inhibition by 1 is downstream of that by ordinary inhibitors. The unique inhibitory action of hydrophobic Deltalac-acetogenins may be closely associated with the dynamic function of the membrane domain of complex I.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mode of Inhibitory Action of Δlac-Acetogenins, a New Class of Inhibitors of Bovine Heart Mitochondrial Complex I

et al. 2006

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“…While both complex I isozymes are presumably capable of performing NADH oxidation and synthesis, there may be differences between the complex I isozymes that explain their predicted relative roles in R. sphaeroides photoheterotrophic growth. For instance, biochemical analysis of complex I A -like enzymes from other bacteria suggest that these enzymes contain two pyridine nucleotide binding sites: one for NADH and one for NAD + ( 4 , 50 – 54 ). In contrast, only a single NADH binding site has been found in the structures of bacterial complex I enzymes ( 12 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

Different Functions of Phylogenetically Distinct Bacterial Complex I Isozymes

et al. 2016

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NADH:quinone oxidoreductase (complex I) is a bioenergetic enzyme that transfers electrons from NADH to quinone, conserving the energy of this reaction by contributing to the proton motive force. While the importance of NADH oxidation to mitochondrial aerobic respiration is well documented, the contribution of complex I to bacterial electron transport chains has been tested in only a few species. Here, we analyze the function of two phylogenetically distinct complex I isozymes in Rhodobacter sphaeroides, an alphaproteobacterium that contains well-characterized electron transport chains. We found that R. sphaeroides complex I activity is important for aerobic respiration and required for anaerobic dimethyl sulfoxide (DMSO) respiration (in the absence of light), photoautotrophic growth, and photoheterotrophic growth (in the absence of an external electron acceptor). Our data also provide insight into the functions of the phylogenetically distinct R. sphaeroides complex I enzymes (complex IA and complex IE) in maintaining a cellular redox state during photoheterotrophic growth. We propose that the function of each isozyme during photoheterotrophic growth is either NADH synthesis (complex IA) or NADH oxidation (complex IE). The canonical alphaproteobacterial complex I isozyme (complex IA) was also shown to be important for routing electrons to nitrogenase-mediated H2 production, while the horizontally acquired enzyme (complex IE) was dispensable in this process. Unlike the singular role of complex I in mitochondria, we predict that the phylogenetically distinct complex I enzymes found across bacterial species have evolved to enhance the functions of their respective electron transport chains.IMPORTANCE Cells use a proton motive force (PMF), NADH, and ATP to support numerous processes. In mitochondria, complex I uses NADH oxidation to generate a PMF, which can drive ATP synthesis. This study analyzed the function of complex I in bacteria, which contain more-diverse and more-flexible electron transport chains than mitochondria. We tested complex I function in Rhodobacter sphaeroides, a bacterium predicted to encode two phylogenetically distinct complex I isozymes. R. sphaeroides cells lacking both isozymes had growth defects during all tested modes of growth, illustrating the important function of this enzyme under diverse conditions. We conclude that the two isozymes are not functionally redundant and predict that phylogenetically distinct complex I enzymes have evolved to support the diverse lifestyles of bacteria.

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