Journal of Bioenergetics and Biomembranes

, Volume 37, Issue 4, pp 207–225

Gradual Alteration of Mitochondrial Structure and Function by β-Amyloids: Importance of Membrane Viscosity Changes, Energy Deprivation, Reactive Oxygen Species Production, and Cytochrome c Release

  • A. M. Aleardi
  • G. Benard
  • O. Augereau
  • M. Malgat
  • J. C. Talbot
  • J. P. Mazat
  • T. Letellier
  • J. Dachary-Prigent
  • G. C. Solaini
  • R. Rossignol
Article

DOI: 10.1007/s10863-005-6631-3

Cite this article as:
Aleardi, A.M., Benard, G., Augereau, O. et al. J Bioenerg Biomembr (2005) 37: 207. doi:10.1007/s10863-005-6631-3

Abstract

Intracellular amyloid beta-peptide (Aβ) accumulation is considered to be a key pathogenic factor in sporadic Alzheimer’s disease (AD), but the mechanisms by which it triggers neuronal dysfunction remain unclear. We hypothesized that gradual mitochondrial dysfunction could play a central role in both initiation and progression of sporadic AD. Thus, we analyzed changes in mitochondrial structure and function following direct exposure to increasing concentrations of Aβ1−42 and Aβ25−35 in order to look more closely at the relationships between mitochondrial membrane viscosity, ATP synthesis, ROS production, and cytochrome c release. Our results show the accumulation of monomeric Aβ within rat brain and muscle mitochondria. Subsequently, we observed four different and additive modes of action of Aβ, which were concentration dependent: (i) an increase in mitochondrial membrane viscosity with a concomitant decrease in ATP/O, (ii) respiratory chain complexes inhibition, (iii) a potentialization of ROS production, and (iv) cytochrome c release.

Keywords

Alzheimer’s disease amyloid-β peptide threshold effect oxidative phosphorylation membrane fluidity cytochrome c release 

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • A. M. Aleardi
    • 1
    • 2
  • G. Benard
    • 2
  • O. Augereau
    • 2
  • M. Malgat
    • 2
  • J. C. Talbot
    • 3
  • J. P. Mazat
    • 2
  • T. Letellier
    • 2
  • J. Dachary-Prigent
    • 2
  • G. C. Solaini
    • 1
  • R. Rossignol
    • 2
  1. 1.Scuola Superiore Sant’AnnaPisaItaly
  2. 2.INSERM, U688 Physiopathologie MitochondrialeUniversité Victor Segalen-Bordeaux 2BordeauxFrance
  3. 3.Institut de Biochimie et Génétique Cellulaires du Centre National de la Recherche Scientifique, UMR5095Université Victor Segalen Bordeaux 2BordeauxFrance