Attempts to define distinct parts of NADH: Ubiquinone oxidoreductase (complex I)

Friedrich, Thorsten; Weidner, Uwe; Nehls, Uwe; Fecke, Wolfgang; Schneider, Ralf; Weiss, Hanns

doi:10.1007/bf00762458

Cited by 40 publications

(32 citation statements)

References 31 publications

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“…The membrane domain has a row of four modules with similarities to Na + /H + antiporter that are assumed to catalyze proton transport. Whether or not sodium ions are transported as well is still a matter of debate (20)(21)(22)(23)(24)(25)(26)(27)(28). Complex I is an example of an energy-converting enzyme with a modular structure composed of an electron donor/transfer module (encoded by nuoE, F, and G), connecting module (encoded by nuoC, D, B, and I), and intrinsic membrane module (encoded by nuoH, N, A, M, K, L, and J).…”

Section: Discussionmentioning

confidence: 99%

Energy conservation by oxidation of formate to carbon dioxide and hydrogen via a sodium ion current in a hyperthermophilic archaeon

Lim

Mayer

Kang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Thermococcus onnurineus NA1 is known to grow by the anaerobic oxidation of formate to CO 2 and H 2 , a reaction that operates near thermodynamic equilibrium. Here we demonstrate that this reaction is coupled to ATP synthesis by a transmembrane ion current. Formate oxidation leads to H + translocation across the cytoplasmic membrane that then drives Na + translocation. The ion-translocating electron transfer system is rather simple, consisting of only a formate dehydrogenase module, a membrane-bound hydrogenase module, and a multisubunit Na + /H + antiporter module. The electrochemical Na + gradient established then drives ATP synthesis. These data give a mechanistic explanation for chemiosmotic energy conservation coupled to formate oxidation to CO 2 and H 2 . Because it is discussed that the membrane-bound hydrogenase with the Naantiporter module are ancestors of complex I of mitochondrial and bacterial electron transport these data also shed light on the evolution of ion transport in complex I-like electron transport chains.ormate is a common end product of bacterial fermentation and is liberated into the environment. It does not accumulate but is oxidized under oxic as well as anoxic conditions. Oxidation of formate to CO 2 and H 2 under anoxic conditions according tois an endergonic process under standard conditions at 25°C. Nevertheless, some anaerobic microbes can grow by this reaction. In anaerobic syntrophic formate oxidation the reaction is made thermodynamically possible by removal of the end product H 2 by a methanogenic or sulfate-reducing partner (1-4). For pure cultures, growth at the expense of Eq. 1 was considered impossible owing to the thermodynamic constraints (2, 3). However, recently we reported that several hyperthermophilic archaea belonging to the family Thermococcales, including Thermococcus onnurineus NA1, are able to grow by oxidation of formate to molecular hydrogen (5, 6). At 80°C, the optimum growth temperature for these hyperthermophiles, the reaction becomes slightly exergonic (ΔG 0 = −2.6 kJ/mol), according to the Van't Hoff equation (7). Measurements of pool sizes of products and educts of the reaction catalyzed by whole cells at 80°C revealed that the ΔG was more negative and growth occurred within a range of concentrations of products and educts that equals −20 to −8 kJ/mol (5), indicating that the reaction is potentially able to drive formation of an electrochemical ion gradient across the membrane.Molecular and genetic analyses revealed that the hydrogenase genes in the fdh2-mfh2-mnh2 gene cluster are essential for growth coupled to formate oxidization and hydrogen production (5, 8). Based on these findings a model was developed in which the formate dehydrogenase (Fdh2) module oxidizes formate; the hydrogenase (Mfh2) module transfers electrons to protons, thereby generating a proton gradient across the membrane that is then used by the Mnh2 module to produce a secondary sodium ion gradient that then drives ATP synthesis, catalyzed by a Na + -ATP synthase (2, 5). In this work...

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Section: Discussionmentioning

confidence: 99%

Energy conservation by oxidation of formate to carbon dioxide and hydrogen via a sodium ion current in a hyperthermophilic archaeon

Lim

Mayer

Kang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The lack of a high-resolution structure of complex I makes it tempting to speculate about the mechanism of proton translocation by looking at the known structures of soluble hydrogenases which are homologous to complex I [Ahlers et al, 2000;Albracht, 1993;Brandt et al, 2003;Friedrich et al, 1993Friedrich et al, , 1995Zickermann et al, 2003]. A model for the ligation and the close environment of N2 can be derived by taking the proximal Fe/S cluster of the small subunit of the hydrogenases for cluster N2 of complex I and by placing the functionally important amino acids identifi ed by FT-IR spectroscopy and site-directed mutagenesis at the corresponding positions using the structure of the small hydrogenases subunit as template ( fi g. 8 ).…”

Section: A Model For Redox-driven Proton Translocation Involving N2mentioning

confidence: 99%

A Possible Role for Iron-Sulfur Cluster N2 in Proton Translocation by the NADH:Ubiquinone Oxidoreductase (Complex I)

et al. 2005

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The proton-pumping NADH:ubiquinone oxidoreductase, the respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. The enzyme mechanism is still unknown due to the lack of a high-resolution structure and its complicated composition. The complex from Escherichia coli is made up of 13 subunits called NuoA through NuoN and contains one FMN and nine iron-sulfur (Fe/S) clusters as redox groups. The pH dependence of the midpoint redox potential of the Fe/S cluster named N2 and its spin-spin interaction with ubiquinone radicals made it an ideal candidate for a key component in redox-driven proton translocation. During the past years we have assigned the subunit localization of cluster N2 to subunit NuoB by site-directed mutagenesis and predicted its ligation by molecular simulation. Redox-induced FT-IR spectroscopy has shown that its redox reaction is accompanied by the protonation and deprotonation of individual amino acid residues. These residues have been identified by site-directed mutagenesis. The enzyme catalytic activity depends on the presence of cluster N2 and is coupled with major conformational changes. From these data a model for redox-induced conformation-driven proton translocation has been derived.

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“…Mammalian complex I consists of about 46 subunits, and seven of them-designated ND1, -2, -3, -4, -4L, -5, and -6-are encoded by mitochondrial DNA (mtDNA) (12,23). A series of biochemical, electron microscopic, and functional investigations have led to a model of the structure of complex I in Neurospora crassa, which contains 32 subunits (17,20,26,53). It is suggested to have an L-shaped structure consisting two complementary moieties: one membrane domain and a peripheral arm protruding to the matrix space.…”

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confidence: 99%

Nuclear Suppression of Mitochondrial Defects in Cells without the ND6 Subunit

Deng

Park

et al. 2006

Molecular and Cellular Biology

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Previously, we characterized a mouse cell line, 4A, carrying a mitochondrial DNA mutation in the subunit for respiratory complex I, NADH dehydrogenase, in the ND6 gene. This mutation abolished the complex I assembly and disrupted the respiratory function of complex I. We now report here that a galactose-resistant clone, 4AR, was isolated from the cells carrying the ND6 mutation. 4AR still contained the homoplasmic mutation, and apparently there was no ND6 protein synthesis, whereas the assembly of other complex I subunits into complex I was recovered. Furthermore, the respiratory activity and mitochondrial membrane potential were fully recovered. To investigate the genetic origin of this compensation, the mitochondrial DNA (mtDNA) from 4AR was transferred to a new nuclear background. The transmitochondrial lines failed to grow in galactose medium. We further transferred mtDNA with a nonsense mutation at the ND5 gene to the 4AR nuclear background, and a suppression for mitochondrial deficiency was observed. Our results suggest that change(s) in the expression of a certain nucleus-encoded factor(s) can compensate for the absence of the ND6 or ND5 subunit.The mammalian respiratory NADH-ubiquinone oxidoreductase (complex I) is the largest and least understood component of the mitochondrial oxidative phosphorylation system (35,50). Located in the inner mitochondrial membrane, complex I is the major entry point for electrons to get into the respiratory chain. It couples electron transfer with the translocation of protons across the membrane, generating a proton gradient that is essential for ATP synthesis. Mammalian complex I consists of about 46 subunits, and seven of them-designated

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Attempts to define distinct parts of NADH: Ubiquinone oxidoreductase (complex I)

Cited by 40 publications

References 31 publications

Energy conservation by oxidation of formate to carbon dioxide and hydrogen via a sodium ion current in a hyperthermophilic archaeon

Energy conservation by oxidation of formate to carbon dioxide and hydrogen via a sodium ion current in a hyperthermophilic archaeon

A Possible Role for Iron-Sulfur Cluster N2 in Proton Translocation by the NADH:Ubiquinone Oxidoreductase (Complex I)

Nuclear Suppression of Mitochondrial Defects in Cells without the ND6 Subunit

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