title: Superoxide production by cytochrome bc1 complex: a mathematical model.
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.
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Guillaud
authors.affiliation: Molecular Bioenergetics Group, Medical School, Goethe University, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dröse
authors.affiliation: Theoretische Biophysik, Humboldt University, Invalidenstraße 42, 10115, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kowald
authors.affiliation: 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.
authors.forename: U
authors.initials: U
authors.lastname: Brandt
authors.affiliation: Theoretische Biophysik, Humboldt University, Invalidenstraße 42, 10115, Berlin, Germany. Electronic address: edda.klipp@rz.hu-berlin.de.
authors.forename: E
authors.initials: E
authors.lastname: Klipp
mesh_terms: D000968:Antimycin A / Q000494:pharmacology; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D051336:Mitochondrial Membranes / Q000378:metabolism; D008962:Models, Theoretical; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D000968:Antimycin A; D014450:Electron Transport Complex III
keywords: Antimycin A; Complex III; Mathematical model; Reactive oxygen species; Superoxide