α-Synuclein induced mitochondrial dysfunction via cytochrome c oxidase subunit 2 in SH-SY5Y cells

• Published in: Experimental cell research Vol. 378; no. 1; pp. 57 - 65
• Main Authors: Danyu, Lin, Yanran, Liang, Xiuna, Jing, Ying, Chen, Sudan, Peng, Tianen, Zhou, Zhifen, Zeng, Dezhi, Zheng, Kaixun, Huang, Yingyu, Xie, Enxiang, Tao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2019
• Subjects: alpha-Synuclein - metabolism; Cell Line, Tumor; Cytochrome c oxidase subunit 2; Cytochromes c - metabolism; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; Humans; Membrane Potential, Mitochondrial; Mitochondria - metabolism; Mitochondrial dysfunction; Neurons - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reactive Oxygen Species - metabolism; SH-SY5Y cells; α-Synuclein; α-Synuclein; Mitochondrial dysfunction; Cytochrome c oxidase subunit 2; SH-SY5Y cells
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2019.02.006

The transfer of misfolded α-Synuclein (α-Syn) from cell to cell as a prion protein is important in α-Synucleinopathies. Extraneous α-Syn induces apoptosis of dopaminergic neurons by causing mitochondrial dysfunction. However, the mechanism by which α-Syn disrupts the mitochondrial function is still unclear. In the present study, we used a gene microarray and western blotting analysis to show that the expression of mitochondrially encoded cytochrome c oxidase subunit 2 (MT-CO2, COXII) increased significantly in SH-SY5Y cells stimulated by α-Syn for 24 h. Furthermore, the decline in ATP levels, the decreased mitochondrial membrane potential, and the enhanced reactive oxygen species in cells treated by α-Syn was reversed by inhibiting MT-CO2 gene expression. Subsequently, we observed that upregulation of MT-CO2 contributed to the release of cytochrome c and altered the levels of certain mitochondria-localized proteins, such as BCL2 family proteins. Therefore, we hypothesized that after being transferred into dopaminergic neurons, α-Syn injures mitochondria via activating MT-CO2. Our results suggested the initial step of the process by which α-Syn injures dopaminergic neurons and provides new therapeutic targets for α-Syn associated neurodegenerative disorders.