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Molecular Mechanisms of Superoxide Production by the Mitochondrial Respiratory Chain

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Book cover Mitochondrial Oxidative Phosphorylation

Part of the book series: Advances in Experimental Medicine and Biology ((volume 748))

Abstract

The mitochondrial respiratory chain is a major source of reactive oxygen species (ROS) in eukaryotic cells. Mitochondrial ROS production associated with a dysfunction of respiratory chain complexes has been implicated in a number of degenerative diseases and biological aging. Recent findings suggest that mitochondrial ROS can be integral components of cellular signal transduction as well. Within the respiratory chain, complexes I (NADH:ubiquinone oxidoreductase) and III (ubiquinol:cytochrome c oxidoreductase; cytochrome bc 1 complex) are generally considered as the main producers of superoxide anions that are released into the mitochondrial matrix and the intermembrane space, respectively. The primary function of both respiratory chain complexes is to employ energy supplied by redox reactions to drive the vectorial transfer of protons into the mitochondrial intermembrane space. This process involves a set of distinct electron carriers designed to minimize the unwanted leak of electrons from reduced cofactors onto molecular oxygen and hence ROS generation under normal circumstances. Nevertheless, it seems plausible that superoxide is derived from intermediates of the normal catalytic cycles of complexes I and III. Therefore, a detailed understanding of the molecular mechanisms driving these enzymes is required to understand mitochondrial ROS production during oxidative stress and redox signalling. This review summarizes recent findings on the chemistry and control of the reactions within respiratory complexes I and III that result in increased superoxide generation. Regulatory contributions of other components of the respiratory chain, especially complex II (succinate:ubiquinone oxidoreductase) and the redox state of the ubiquinone pool (Q-pool) will be briefly discussed.

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Acknowledgements

We thank Lea Bleier, Volker Zickermann and Klaus Zwicker for careful and critical reading of our manuscript and for helpful discussion. Funding by the Deutsche Forschungsgemeinschaft, SFB815 Project A2, and the BMBF project 0315584A: GerontoMitoSys, is gratefully acknowledged. This study was also supported by the Excellence Initiative of the German Federal and State Governments (EXC 115).

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  1. Molecular Bioenergetics Group, Medical School, Cluster of Excellence Frankfurt “Macromolecular Complexes”, Center for Membrane Proteomics, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany

    Stefan Dröse & Ulrich Brandt

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  1. Stefan Dröse
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  2. Ulrich Brandt
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Correspondence to Stefan Dröse .

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  1. Philipps-Universitaet Marburg, Marburg, 35032, Germany

    Bernhard Kadenbach

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Dröse, S., Brandt, U. (2012). Molecular Mechanisms of Superoxide Production by the Mitochondrial Respiratory Chain. In: Kadenbach, B. (eds) Mitochondrial Oxidative Phosphorylation. Advances in Experimental Medicine and Biology, vol 748. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3573-0_6

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