Superoxide production by cytochrome bc1 complex: a mathematical model

F Guillaud; S Dröse; A Kowald; U Brandt; E Klipp

doi:10.1016/j.bbabio.2014.05.358

Superoxide production by cytochrome bc1 complex: a mathematical model

Biochim Biophys Acta. 2014 Oct;1837(10):1643-52. doi: 10.1016/j.bbabio.2014.05.358. Epub 2014 Jun 7.

Authors

F Guillaud¹, S Dröse², A Kowald³, U Brandt⁴, E Klipp⁵

Affiliations

¹ Theoretische Biophysik, Humboldt University, Invalidenstraße 42, 10115, Berlin, Germany; INSERM U1082, University of Poitiers, Faculty of Medicine and Pharmacy, CHU of Poitiers, 6 rue de la Milétrie, 86021 Poitiers, France.
² Molecular Bioenergetics Group, Medical School, Goethe University, Frankfurt am Main, Germany.
³ Theoretische Biophysik, Humboldt University, Invalidenstraße 42, 10115, Berlin, Germany.
⁴ Molecular Bioenergetics Group, Medical School, Goethe University, Frankfurt am Main, Germany; Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Centre, Geert Grooteplein-Zuid 10, 6525GA Nijmegen, The Netherlands.
⁵ Theoretische Biophysik, Humboldt University, Invalidenstraße 42, 10115, Berlin, Germany. Electronic address: [email protected].

PMID: 24911293
DOI: 10.1016/j.bbabio.2014.05.358

Abstract

Reactive oxygen species (ROS) are involved in the pathophysiology of several diseases (e.g. Alzheimer or atherosclerosis) and also in the aging process. The main source of ROS in aerobic organisms is the electron transport chain (ETC) in the inner mitochondrial membrane. Superoxide is produced at complexes I and III of the ETC, starting a complex network of ROS reactions. To achieve a deeper mechanistic understanding of how ROS are generated by complex III, we developed a mathematical model that successfully describes experimental data of complex III activity in various rat tissues, the production of ROS with and without antimycin and ROS generation depending on different values of the membrane potential ∆Ψ. The model also reinforces the idea of ubiquinone acting as a redox mediator between heme bL and oxygen, as proposed earlier.

Keywords: Antimycin A; Complex III; Mathematical model; Reactive oxygen species; Superoxide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimycin A / pharmacology
Electron Transport
Electron Transport Complex III / antagonists & inhibitors
Electron Transport Complex III / metabolism*
Membrane Potential, Mitochondrial
Mitochondrial Membranes / metabolism
Models, Theoretical*
Reactive Oxygen Species / metabolism
Superoxides / metabolism*

Substances

Reactive Oxygen Species
Superoxides
Antimycin A
Electron Transport Complex III