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.
Keywords: Cytochrome c oxidase subunit 2; Mitochondrial dysfunction; SH-SY5Y cells; α-Synuclein.
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