Amyloid β-Peptide Promotes Permeability Transition Pore in Brain Mitochondria

In this work the effect of the neurotoxic amino acid sequence, Aβ_25–35, on brain mitochondrial permeability transition pore (PTP) was studied. For the purpose, the mitochondrial transmembrane potential (ΔΨm), mitochondrial respiration and the calcium fluxes were examined. It was observed that Aβ_25–35, in the presence of Ca²⁺, decreased the ΔΨm, the capacity of brain mitochondria to accumulate calcium and led to a complete uncoupling of the respiration. However, the reverse sequence of the peptide Aβ_25–35 (Aβ_35–25) did not promote the PTP. The alterations promoted by Aβ_35–25 and/or Ca²⁺ could be reversed when Ca²⁺ was removed by EGTA or when ADP plus oligomycin were present. The pre-treatment with CsA or ADP plus oligomycin prevented the ΔΨm drop and preserved the capacity of mitochondria to accumulate Ca²⁺. These results suggest that Aβ_25–35 can promote the PTP induced by Ca²⁺.