Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells

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Abstract

Alpha-synuclein (alpha-syn) is implicated in the pathogenesis of Parkinson's disease (PD). Mutations in alpha-syn gene or alpha-syn locus (SNCA) triplication are associated with mitochondrial abnormalities and early onset of familial PD. The goals of the present study were to examine whether alpha-syn is localized in the mitochondria of alpha-syn overexpressing cells (HEK-syn cells); and whether alpha-syn overexpression causes cells to be more vulnerable to mitochondrial toxin, rotenone. Western blotting and confocal microscopy techniques were employed to assess localization of alpha-syn in the mitochondria of HEK-293 cells that were stably transfected with human wild-type alpha-syn. The results demonstrated that the mitochondrial fractions that were isolated from HEK-syn cells showed the presence of alpha-syn, whereas, no alpha-syn was detected in the mitochondrial fractions of control HEK cells. The mitochondria of HEK-syn cells were found to be more susceptible to rotenone-induced toxicity when compared to control HEK cells. The intracellular ATP levels were significantly decreased in HEK-syn cells in response to sub toxic concentrations of rotenone. These results suggest that under overexpression conditions, alpha-syn may translocate to mitochondria and cause enhanced toxicity in response to sub toxic concentrations of mitochondrial toxins. This study has implications to the pathogenesis of familial PD where alpha-syn overexpression is mainly involved. © 2008 Elsevier Ireland Ltd. All rights reserved.

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Shavali, S., Brown-Borg, H. M., Ebadi, M., & Porter, J. (2008). Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells. Neuroscience Letters, 439(2), 125–128. https://doi.org/10.1016/j.neulet.2008.05.005

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