a-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson's disease

This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human a-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, a-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type a-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria. The results are significant in view of the fact that a-synucleinopathy is involved in the pathogenesis of Parkinson's disease.