MTERF4 regulates the mitochondrial dysfunction induced by MPP+ in SH-SY5Y cells

作者：Ye, Xiaofei; Han, Yanyan; Zhang, Linbing; Liu, Wen^*; Zuo, Ji

来源：Biochemical and Biophysical Research Communications, 2015, 464(1): 214-220.

DOI：10.1016/j.bbrc.2015.06.119

• Mitochondrial transcription termination
• factors 4 (MTERF4)
• mtDNA expression
• Mitochondrial dysfunction
• Parkinson's disease
• MPP+

Mitochondrial transcription termination factor 4, MTERF4, a member of the MTERF family, has been implicated in the regulation of mitochondrial translation by targeting NSUN4 to the large mitochondrial ribosome. Here, we found a novel role for MTERF4 in regulating mitochondrial dysfunction induced by MPP+. We observed that knockdown of MTERF4 in SH-SY5Y cells resulted in increased mitochondrial DNA transcription levels and decreased mitochondrial DNA translation levels. In addition, after treatment with 2 mM MPP+ for 24 h, the expression levels of MTERF4 were decreased compared to wide-type SH-SY5Y cells. Moreover, after exposure to 2 mM MPP+ for 24 h, knockdown of MTERF4 in SH-SY5Y cells worsened the mitochondrial dysfunction induced by MPP+, including increased reactive oxygen species, accumulated cleaved PARP-1, decreased mitochondrial membrane potential and depressed mitochondrial complexes. Furthermore, overexpression of MTERF4 in SH-SY5Y cells partially alleviated the mitochondrial dysfunction induced by MPP+. Based on these findings, we suggest that the main function of MTERF4 is regulating mtDNA expression, and it is the crucial factor in the mechanism of mitochondrial dysfunction in SH-SY5Y cells induced by MPP+. MTERF4 probably is the triggering of the pathogenesis of Parkinson's disease induced by environmental toxin.

• 出版日期2015-8-14
• 单位复旦大学