Review
Superoxide generation by complex III: From mechanistic rationales to functional consequences

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Abstract

Apart from complex I (NADH:ubiquinone oxidoreductase) the mitochondrial cytochrome bc1 complex (complex III; ubiquinol:cytochrome c oxidoreductase) has been identified as the main producer of superoxide and derived reactive oxygen species (ROS) within the mitochondrial respiratory chain. Mitochondrial ROS are generally linked to oxidative stress, aging and other pathophysiological settings like in neurodegenerative diseases. However, ROS produced at the ubiquinol oxidation center (center P, Qo site) of complex III seem to have additional physiological functions as signaling molecules during cellular processes like the adaptation to hypoxia. The molecular mechanism of superoxide production that is mechanistically linked to the electron bifurcation during ubiquinol oxidation is still a matter of debate. Some insight comes from extensive kinetic studies with mutated complexes from yeast and bacterial cytochrome bc1 complexes. This review is intended to bridge the gap between those mechanistic studies and investigations on complex III ROS in cellular signal transduction and highlights factors that impact superoxide generation. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.

Highlights

► Different mechanisms of superoxide generation by complex III are discussed. ► Factors that influence the generation and release of ROS are summarized. ► The role of complex III derived ROS as ‘signaling molecules’ is critically reviewed.

Abbreviations

H2O2
hydrogen peroxide
O2radical dot
superoxide
Q
ubiquinone
QH2
ubiquinol
Qradical dot/SQ
semiquinone
Qi site/center N
ubiquinone reduction site
Qo site/center P
ubiquinol oxidation site
ROS
reactive oxygen species
SMPs
submitochondrial particles

Keywords

Complex III
Cytochrome bc1 complex
Mitochondria
Reactive oxygen species
Superoxide
Redox signaling

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This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.