Differential effects of wild-type and A53T mutant isoform of alpha-synuclein on the mitochondrial proteome of differentiated SH-SY5Y cells

Pennington, Kyla and Peng, Jianhe and Hung, Chao-Chun and Banks, Rosamonde E. and Robinson, Philip A. (2010) Differential effects of wild-type and A53T mutant isoform of alpha-synuclein on the mitochondrial proteome of differentiated SH-SY5Y cells. Journal of Proteome Research, 9 (5). pp. 2390-2401. ISSN 1535-3893

Full content URL: http://pubs.acs.org/doi/abs/10.1021/pr901102d

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Differential effects of wild-type and A53T mutant isoform of alpha-synuclein on the mitochondrial proteome of differentiated SH-SY5Y cells

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Abstract

Increased levels of wild-type (WT) R-synuclein (R-syn) and mutant A53T R-syn are associated with Parkinson’s disease (PD), a disease with abnormal mitochondrial function. This study compared mitochondria prepared from differentiated SH-SY5Y cells overexpressing WT or A53T R-syn with control cells, using 2-D difference in-gel electrophoresis. Statistical analysis was carried out primarily using ANOVA (p < 0.01; Host:WT:A53T) and subsequently using independent t tests (host vs WT, host vs A53T). Of the protein spots found to be differentially expressed (n ) 71; p < 0.01, >1.8/<-1.8 fold
change), 63 proteins were identified by LC-MS/MS, with the majority (77%) significantly altered in WT samples only. Twenty-three mitochondrial proteins were abnormally expressed including those with roles in ATP synthesis, oxidoreduction, motor activity, carbohydrate metabolism, protein transcription, and protein folding. Thirteen forms of cytoskeletal proteins were also found to be overexpressed in the mitochondrial preparations from WT R-syn cells, suggesting an increased interaction of mitochondria with the cytoskeletal network. Altered levels of four mitochondrial proteins (HSPA9 (mortalin), NDUFS1, DLAT, ATP5A1) were confirmed using Western blot analysis. Furthermore, a significant reduction in OXPHOS 1 activity was observed in the WT R-syn cells, suggesting that there are functional
consequences of the observed altered protein expression changes in the mitochondria.

Keywords:Parkinson’s disease, alpha-synuclein, mitochondria, 2D-DIGE, A53T, complex I. mortalin, ATP synthase, pyruvate dehydrogenase
Subjects:C Biological Sciences > C800 Psychology
C Biological Sciences > C860 Neuropsychology
Divisions:College of Social Science > School of Psychology
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ID Code:9303
Deposited On:02 May 2013 14:14

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