Significance of respirasomes for the assembly/stability of human respiratory chain complex I.
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.
Schägger
Hermann
H
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
de Coo
René
R
Bauer
Matthias F
MF
Hofmann
Sabine
S
Godinot
Catherine
C
Brandt
Ulrich
U
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
D003902:Detergents; D045303:Cytochromes b; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III