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On the Mechanism of the Respiratory Complex I

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A Structural Perspective on Respiratory Complex I

Abstract

The energy-converting NADH:ubiquinone oxidoreductase, respiratory complex I, couples the electron transfer from NADH to ubiquinone with a proton translocation across the membrane. Electron microscopy revealed the two-part structure of the enzyme complex. A peripheral arm, composed of globular subunits, extends into the aqueous phase. The arm contains the cofactors for the electron transfer reaction, namely one flavin mononucleotide and up to ten iron-sulfur (Fe/S) clusters. The other arm, the membrane arm, is embedded in the lipid bilayer and thus necessarily involved in proton translocation. The (ubi)quinone binding site is most likely located at the interface of the two arms. The oxidation of one NADH is coupled with the translocation of four protons (current consensus value). In this chapter, the binding of the substrates NADH and (ubi)quinone, the role of individual Fe/S clusters and the mechanism of proton translocation are discussed in the light of recent data obtained from our laboratories. We propose a model for the respiratory complex I, in which the electron transfer is coupled with the translocation of two protons by the (ubi)quinone redox chemistry and the residual two protons by conformational changes within the membrane arm.

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Acknowledgment

The work in the authors groups was supported by the Deutsche Forschungsge­meinschaft (DFG; to TF and OE), by the Volkswagen Foundation (to TF and PH) and the Agence Nationale de Recherche (ANR; to PH). We thank Linda Williams for her help in correcting the manuscript.

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  1. Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstr. 21, 79104, Freiburg, Germany

    Thorsten Friedrich & Oliver Einsle

  2. Faculté de chimie, Laboratoire de spectroscopie vibrationelle et électrochimie des biomolécules, Université de Strasbourg, 1 rue Blaise Pascal, 67008, Strasbourg, France

    Petra Hellwig

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  1. Thorsten Friedrich
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  2. Petra Hellwig
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  3. Oliver Einsle
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Correspondence to Thorsten Friedrich .

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  1. , Mitochondrial Biology Unit, Medical Research Council, Hills road, Cambridge, CB2 0XY, Cambridgeshire, United Kingdom

    Leonid Sazanov

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Friedrich, T., Hellwig, P., Einsle, O. (2012). On the Mechanism of the Respiratory Complex I. In: Sazanov, L. (eds) A Structural Perspective on Respiratory Complex I. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4138-6_2

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