title: Pink1/Parkin-mediated mitophagy play a protective role in cisplatin induced renal tubular epithelial cells injury.
abstract: Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. In cultured human renal proximal tubular cells, we found that knockdown of Pink1/Parkin induced the aggravation of mitochondrial function, leading to the increase of cell injury through inhibition of mitophagy. Additionally, the overexpression of Pink1/Parkin protected against cisplatin-induced mitochondrial dysfunction and cell injury by promoting mitophagy. Our results provide clear evidence that Pink1/Parkin-dependent mitophagy has identified potential targets for the treatment of cisplatin-induced AKI.
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Chuanyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Zhuyun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: An
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Suyan
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Chengning
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China; Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China. Electronic address: cyxing62@126.com.
authors.forename: Changying
authors.initials: C
authors.lastname: Xing
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China. Electronic address: ygyuan@njmu.edu.cn.
authors.forename: Yanggang
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D002945:Cisplatin / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology*; D063306:Mitophagy; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D002945:Cisplatin; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
keywords: AKI; Cisplatin; Mitochondrial dysfunction; Mitophagy; Parkin; Pink1