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A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
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Updated: May 2, 2026

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
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Superoxide generation by complex III: from mechanistic rationales to functional consequences.

Lea Bleier1, Stefan Dröse

  • 1Molecular Bioenergetics Group, Medical School, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.

Biochimica Et Biophysica Acta
|December 28, 2012
PubMed
Summary

The mitochondrial cytochrome bc1 complex (complex III) is a major source of superoxide and reactive oxygen species (ROS). These ROS have signaling roles in cellular processes like hypoxia adaptation, beyond links to aging and disease.

Keywords:
Complex IIICytochrome bc(1) complexH(2)O(2)MitochondriaO(2)(−)QQ(i) site/center NQ(o) site/center PQ(−)/SQQH(2)ROSReactive oxygen speciesRedox signalingSMPsSuperoxidehydrogen peroxidereactive oxygen speciessemiquinonesubmitochondrial particlessuperoxideubiquinolubiquinol oxidation siteubiquinoneubiquinone reduction site

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Area of Science:

  • Biochemistry
  • Cellular Biology
  • Mitochondrial Function

Background:

  • Mitochondrial respiratory chain complex III (cytochrome bc1 complex) is a primary source of superoxide and reactive oxygen species (ROS).
  • Mitochondrial ROS are implicated in aging, oxidative stress, and neurodegenerative diseases.
  • ROS generated at complex III's ubiquinol oxidation site (Qo site) may function as signaling molecules, particularly in hypoxia adaptation.

Purpose of the Study:

  • To review the mechanistic studies of superoxide production in complex III.
  • To connect mechanistic insights with cellular signaling functions of complex III-derived ROS.
  • To highlight factors influencing superoxide generation by complex III.

Main Methods:

  • Review of kinetic studies using mutated yeast and bacterial cytochrome bc1 complexes.
  • Analysis of literature on complex III ROS in cellular signal transduction.
  • Synthesis of data from mechanistic and physiological investigations.

Main Results:

  • Complex III is a significant producer of mitochondrial superoxide and ROS.
  • Superoxide production is linked to electron bifurcation during ubiquinol oxidation.
  • Complex III ROS play physiological roles in signaling, such as during hypoxia response.

Conclusions:

  • Understanding the mechanism of ROS production in complex III is crucial.
  • Complex III ROS are key signaling molecules in cellular adaptation.
  • Bridging mechanistic and physiological studies will advance knowledge of ROS function.