PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells

Hongmei Dai, Yuanying Deng, Jie Zhang, Hailong Han, Mingyi Zhao, Ying Li, Chen Zhang, Jing Tian, Guoying Bing, Lingling Zhao

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides. There are links between CPF exposure and neurological disorders. Mitochondrial damage has been implicated to play a key role in CPF-induced neurotoxicity. Mitophagy, the selective autophagic elimination of mitochondria, is an important mitochondrial quality control mechanism. However, the role of mitophagy in CPF-induced neurotoxicity remains unclear. In this study, CPF-caused mitochondrial damage, role and mechanism of mitophagy on CPF-induced neuroapoptosis were extensively studied by using SH-SY5Y cells. We showed that CPF treatment caused mitochondrial fragmentation, excessive ROS generation and mitochondrial depolarization, thus led to cell apoptosis. Moreover, CPF treatment also resulted in increased colocalizaton of mitochondria with LC3, decreased levels of mitochondrial proteins, PINK1 stabilization and mitochondrial accumulation of Parkin. These data suggested that CPF treatment induced PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Furthermore, knockdown of Parkin dramatically increased CPF-induced neuroapoptosis. On the other hand, overexpression of Parkin markedly alleviated CPF-induced SH-SY5Y cell apoptosis. Together, these findings implicate a protective role of PINK1/Parkin-mediated mitophagy against neuroapoptosis and that enhancing mitophagy provides a potential therapeutic strategy for CPF-induced neurological disorders.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalToxicology
Volume334
DOIs
StatePublished - Aug 6 2015

Bibliographical note

Funding Information:
This work was supported by Construction Fund for Key Subjects of Hunan Province (2012) and United Bank of Switzerland-Optimus Foundation ( GIFTS ID 6102 ). We are grateful to academician XIA Jiahui and the staff from the State Key Laboratory of Medical Genetics at Central South University for their excellent technical assistance. Special thanks should go to JIA Sujie for providing language help and writing assistance in proof reading the article.

Publisher Copyright:
© 2015.

Keywords

  • Apoptosis
  • Chlorpyrifos
  • Mitophagy
  • PINK1/Parkin

ASJC Scopus subject areas

  • Toxicology

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