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β‐Amyloid fragment 25–35 selectively decreases complex IV activity in isolated mitochondria
Author(s) -
Canevari Laura,
Clark John B,
Bates Timothy E
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01028-5
Subject(s) - mitochondrion , cytochrome c oxidase , proteolysis , extracellular , biochemistry , mitochondrial respiratory chain , amyloid beta , respiratory chain , amyloid precursor protein , chemistry , amyloid (mycology) , cytochrome c , peptide , p3 peptide , intracellular , alzheimer's disease , biology , enzyme , medicine , disease , inorganic chemistry
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 β‐amyloid toxicity. Recent evidence suggests that the proteolysis of APP to generate β‐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 β‐amyloid fragment 25–35 (100 μM) 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, while 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.