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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.<\/jats:p>","DOI":"10.1038\/s41419-018-1152-2","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T12:25:54Z","timestamp":1541075154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":174,"title":["PINK1\/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury"],"prefix":"10.1038","volume":"9","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyuan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuohua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"1152_CR1","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nrd1691","volume":"4","author":"D Wang","year":"2005","unstructured":"Wang, D. & Lippard, S. 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