title: Mitochondrial respiratory chain Complexes I and IV are impaired by β-amyloid via direct interaction and through Complex I-dependent ROS production, respectively.
abstract: Here we investigate the effect of β-amyloid on mitochondrial respiratory function, i.e. mitochondrial oxygen consumption and membrane potential generation as well as the individual activities of both the mitochondrial Complexes I-IV, that compose mitochondrial electron transport chain, and the ATP synthase, by using homogenate from cerebellar granule cells, treated with low concentrations of β-amyloid, and Alzheimer synaptic-enriched brain samples. We found that β-amyloid caused both a selective defect in Complex I activity associated with an increase (5 fold) of intracellular reactive oxygen species and an impairment of Complex IV likely due to membrane lipid peroxidation. In addition, a 130% increase of the GSSG/GSH ratio was measured in Alzheimer brains with respect to age-matched controls. Knowing the mechanisms of action of β-amyloid could allow to mitigate or even to interrupt the toxic cascade that leads a cell to death. The results of this study represent an important innovation because they offer the possibility to act at mitochondrial level and on specific sites to protect cells, for example by preventing the interaction of β-amyloid with the identified targets, by stabilizing or by restoring mitochondrial function or by interfering with the energy metabolism.
authors.affiliation: Istituto di Biomembrane e Bioenergetica, CNR, Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bobba
authors.forename: G
authors.initials: G
authors.lastname: Amadoro
authors.forename: D
authors.initials: D
authors.lastname: Valenti
authors.forename: V
authors.initials: V
authors.lastname: Corsetti
authors.forename: R
authors.initials: R
authors.lastname: Lassandro
authors.forename: A
authors.initials: A
authors.lastname: Atlante
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000473:pathology; D042967:Electron Transport Complex I / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I