Amyloid ß-Peptide Promotes Permeability Transition Pore in Brain Mitochondria

Abstract

In this work the effect of the neurotoxic amino acid sequence, Aß25–35, on brain mitochondrial permeability transition pore (PTP) was studied. For the purpose, the mitochondrial transmembrane potential (??m), mitochondrial respiration and the calcium fluxes were examined. It was observed that Aß25–35, in the presence of Ca2+, decreased the ??m, the capacity of brain mitochondria to accumulate calcium and led to a complete uncoupling of the respiration. However, the reverse sequence of the peptide Aß25–35 (Aß35–25) did not promote the PTP. The alterations promoted by Aß35–25 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 ??m drop and preserved the capacity of mitochondria to accumulate Ca2+. These results suggest that Aß25–35 can promote the PTP induced by Ca2+.