Characteristics of the mitocondrial permeability transition in brain cortex mitocondria.

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Summary *

Mitochondria protect neurons from the deleterious effects of abnormal Ca2+ influx, which leads to the activation of hydrolytic and degradation pathways associated with apoptosis and necrosis. In this work different characteristics of the MPT in mouse non synaptic brain cortex mitochondria were studied. Methodological approaches for MPT characterization will be described. Mitochondrial swelling and membrane potential were evaluated after a single bolus of 100 mM Ca2+ addition. Respiratory function and production of reactive oxygen derived molecules, were analysed before and after calcium induction of MPT. Energized organelles after MPT induction with 100 mM Ca2+, showed mitochondrial depolarization and partial swelling that was maximal after addition of alamethicin. Mitochondrial swelling induced by 100 mM Ca2+ was associated with an impaired respiratory function. Mitochondrial hydrogen peroxide (H2O2) production, dependent of a high proton force was increased after 100 mM Ca2+ or alamethicin. Mitochondrial CsA pretreatment was able to restore respiratory function transmembrane potential and H2O2 levels to those observed in untreated mitochondria. As expected, alamethicin alone or with 100 mM Ca2+ induced swelling accompanied by a clear mitochondrial depolarization, a 113% increase in state 4 respiratory rate and a 66% decrease in state 3 respiratory rate. The effect of NO on MPT and apoptotic cell death will be discussed, as well as the role of MPT induction in brain pathology. Information provided by the agent in SIGEVA