Mitochondrial respiratory chain super-complex I-III in physiology and pathology.
Recent investigations by native gel electrophoresis showed the existence of supramolecular associations of the respiratory complexes, confirmed by electron microscopy analysis and single particle image processing. Flux control analysis demonstrated that Complex I and Complex III in mammalian mitochondria kinetically behave as a single unit with control coefficients approaching unity for each component, suggesting the existence of substrate channeling within the super-complex. The formation of this supramolecular unit largely depends on the lipid content and composition of the inner mitochondrial membrane. The function of the super-complexes appears not to be restricted to kinetic advantages in electron transfer: we discuss evidence on their role in the stability and assembly of the individual complexes, particularly Complex I, and in preventing excess oxygen radical formation. There is increasing evidence that disruption of the super-complex organization leads to functional derangements responsible for pathological changes, as we have found in K-ras-transformed fibroblasts.
Lenaz
Giorgio
G
Dipartimento di Biochimica, Università di Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Baracca
Alessandra
A
Barbero
Giovanna
G
Bergamini
Christian
C
Dalmonte
Maria Elena
ME
Del Sole
Marianna
M
Faccioli
Marco
M
Falasca
Anna
A
Fato
Romana
R
Genova
Maria Luisa
ML
Sgarbi
Gianluca
G
Solaini
Giancarlo
G
D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000737:chemistry / Q000502:physiology*; D042967:Electron Transport Complex I / Q000737:chemistry / Q000502:physiology; D042963:Electron Transport Complex II / Q000737:chemistry / Q000502:physiology; D014450:Electron Transport Complex III / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000473:pathology / Q000503:physiopathology; D008954:Models, Biological; D055503:Protein Multimerization; D055550:Protein Stability; D017382:Reactive Oxygen Species / Q000378:metabolism
D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III