title: beta-Amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria.
abstract: Defects in mitochondrial oxidative metabolism, in particular decreased activity of cytochrome c oxidase, have been demonstrated in Alzheimer's disease, and after the expression of the amyloid precursor protein (APP) in cultured cells, suggesting that mitochondria might be involved in beta-amyloid toxicity. Recent evidence suggests that the proteolysis of APP to generate beta-amyloid is at least in part intracellular, preceding the deposition of extracellular fibrils. We have therefore investigated the effect of incubation of isolated rat brain mitochondria with the beta-amyloid fragment 25-35 (100 microM) on the activities of the mitochondrial respiratory chain complexes I, II-III, IV (cytochrome c oxidase) and citrate synthase. The peptide caused a rapid, dose-dependent decrease in the activity of complex IV, white it had no effect on the activities on any of the other enzymes tested. The reverse sequence peptide (35-25) had no effect on any of the activities measured. We conclude that inhibition of mitochondrial complex IV might be a contributing factor to the pathogenesis of Alzheimer's disease.
authors.affiliation: Department of Neurochemistry, Institute of Neurology, London, UK. l.canevari@ion.ucl.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Canevari
authors.forename: J B
authors.initials: JB
authors.lastname: Clark
authors.forename: T E
authors.initials: TE
authors.lastname: Bates
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase