Gradual alteration of mitochondrial structure and function by beta-amyloids: importance of membrane viscosity changes, energy deprivation, reactive oxygen species production, and cytochrome c release

J Bioenerg Biomembr. 2005 Aug;37(4):207-25. doi: 10.1007/s10863-005-6631-3.


Intracellular amyloid beta-peptide (A beta) 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 A beta(1--42) and A beta(25--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 A beta within rat brain and muscle mitochondria. Subsequently, we observed four different and additive modes of action of A beta, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • Brain / drug effects
  • Brain / enzymology
  • Brain / metabolism
  • Brain / ultrastructure
  • Cytochromes c / metabolism*
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / enzymology
  • Intracellular Membranes / metabolism
  • Male
  • Membrane Fluidity / drug effects
  • Mitochondria, Muscle / drug effects*
  • Mitochondria, Muscle / enzymology
  • Mitochondria, Muscle / metabolism
  • Oxygen Consumption / drug effects
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Viscosity


  • Amyloid beta-Peptides
  • Antioxidants
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (25-35)
  • Adenosine Triphosphate
  • Cytochromes c
  • Prostaglandin-Endoperoxide Synthases