role of alpha-synuclein protein levels in mitochondrial morphology and cell survival in cell linesα-突触核蛋白的蛋白质含量在细胞系细胞线粒体形态和生存.pdfVIP

Role of Alpha-Synuclein Protein Levels in Mitochondrial Morphology and Cell Survival in Cell Lines 1,2,3 1,2,3 2 Min Zhu , Wenwei Li *, Chuanzhen Lu * 1 Laboratory for Neurology of Institute of Integrative Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, P. R. China, 2 Institute of Neurology and Huashan Hospital, Fudan University Shanghai Medical College, Shanghai, P. R. China, 3 State Key Laboratory of Medical Neurobiology, Fudan University Shanghai Medical College, Shanghai, P. R. China Abstract a-Synuclein is highly associated with some neurodegeneration and malignancies. Overexpressing wild-type or mutant a- synuclein promotes neuronal death by mitochondrial dysfunction, the underlying mechanisms of which remain poorly defined. It was recently reported that a-synuclein expression could directly lead to mitochondrial fragmentation in vitro and in vivo, which may be due to a-synuclein localization on mitochondria. Here, we applied a double staining method to demonstrate mitochondrial morphogenetic changes in cells overexpressed with a-synuclein. We show that mitochondrial localization of a-synuclein was increased following its overexpression in three distinct cell lines, including HeLa, SH-SY5Y, and PC12 cells, but no alteration in mitochondrial morphology was detected. However, a-synuclein knockdown prevents MPP+-induced mitochondrial fragmentation in SH-SY5Y and PC12 cells. These data suggest that a-synuclein protein levels hardly affect mitochondrial morphology in normal cell lines, but may have some influence on that under certain environmental conditions. Citation: Zhu M, Li W, Lu C (2012) Role of Alpha-Synuclein Protein Levels in Mitochondrial Morphology and Cell Survival in Cell Line