title: Significance of respirasomes for the assembly/stability of human respiratory chain complex I.
abstract: We showed that the human respiratory chain is organized in supramolecular assemblies of respiratory chain complexes, the respirasomes. The mitochondrial complexes I (NADH dehydrogenase) and III (cytochrome c reductase) form a stable core respirasome to which complex IV (cytochrome c oxidase) can also bind. An analysis of the state of respirasomes in patients with an isolated deficiency of single complexes provided evidence that the formation of respirasomes is essential for the assembly/stability of complex I, the major entry point of respiratory chain substrates. Genetic alterations leading to a loss of complex III prevented respirasome formation and led to the secondary loss of complex I. Therefore, primary complex III assembly deficiencies presented as combined complex III/I defects. This dependence of complex I assembly/stability on respirasome formation has important implications for the diagnosis of mitochondrial respiratory chain disorders.
authors.affiliation: Institut für Biochemie I, Zentrum der Biologischen Chemie, Fachbereich Medizin, Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. schagger@zbc.kgu.de
authors.forename: Hermann
authors.initials: H
authors.lastname: Schägger
authors.forename: René
authors.initials: R
authors.lastname: de Coo
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Bauer
authors.forename: Sabine
authors.initials: S
authors.lastname: Hofmann
authors.forename: Catherine
authors.initials: C
authors.lastname: Godinot
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
mesh_terms: D045303:Cytochromes b / Q000235:genetics; D003902:Detergents / Q000494:pharmacology; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation
chemical_list: D003902:Detergents; D045303:Cytochromes b; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III