Amyloid β-peptide promotes permeability transition pore in brain mitochondria

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