PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury

Ying Wang, Chengyuan Tang, Juan Cai, Guochun Chen, Dongshan Zhang, Zhuohua Zhang, Zheng Dong

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cisplatin is a widely used chemotherapeutic drug with notorious toxicity in the kidneys, which involves mitochondrial dysfunction and damage in renal tubular cells. Mitophagy is a form of selective autophagy that removes damaged or dysfunctional mitochondria to maintain cellular homeostasis. In this study, we have used mouse and cell models to examine the role and regulation of mitophagy in cisplatin nephrotoxicity. Cisplatin treatment was associated with the activation of autophagy and mitophagy. Rapamycin, a pharmacological inhibitor of mTOR, stimulated autophagy and mitophagy, and alleviated the development of cisplatin nephrotoxicity. PINK1 and Parkin were increased in kidney tissues during cisplatin treatment of mice. In PINK1 or Parkin gene knockout mouse models, both basal and cisplatin-induced mitophagy in kidneys were defective. Compared with wild-type littermates, PINK1 and Parkin knockout mice showed more severe renal functional loss, tissue damage, and apoptosis during cisplatin treatment. The results suggest that PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity and has a protective role against kidney injury.

Original languageEnglish (US)
Article number1113
JournalCell Death and Disease
Volume9
Issue number11
DOIs
StatePublished - Nov 1 2018

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Mitochondrial Degradation
Cisplatin
Kidney
Wounds and Injuries
Autophagy
Knockout Mice
Gene Knockout Techniques
Sirolimus
Mitochondria
Homeostasis
Pharmacology
Apoptosis

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury. / Wang, Ying; Tang, Chengyuan; Cai, Juan; Chen, Guochun; Zhang, Dongshan; Zhang, Zhuohua; Dong, Zheng.

In: Cell Death and Disease, Vol. 9, No. 11, 1113, 01.11.2018.

Research output: Contribution to journalArticle

Wang, Ying ; Tang, Chengyuan ; Cai, Juan ; Chen, Guochun ; Zhang, Dongshan ; Zhang, Zhuohua ; Dong, Zheng. / PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury. In: Cell Death and Disease. 2018 ; Vol. 9, No. 11.
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