@article{04ca2968ff5c48a9b5cf23e60734e3b3,
title = "PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury",
abstract = "Damaged or dysfunctional mitochondria are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Therefore, timely removal of these organelles is critical to cellular homeostasis and viability. Mitophagy is the mechanism of selective degradation of mitochondria via autophagy. The significance of mitophagy in kidney diseases, including ischemic acute kidney injury (AKI), has yet to be established, and the involved pathway of mitophagy remains poorly understood. Here, we show that mitophagy is induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI. Mitophagy under these conditions is abrogated by Pink1 and Park2 deficiency, supporting a critical role of the PINK1-PARK2 pathway in tubular cell mitophagy. Moreover, ischemic AKI is aggravated in pink1 andpark2 single- as well as double-knockout mice. Mechanistically, Pink1 and Park2 deficiency enhances mitochondrial damage, reactive oxygen species production, and inflammatory response. Taken together, these results indicate that PINK1-PARK2-mediated mitophagy plays an important role in mitochondrial quality control, tubular cell survival, and renal function during AKI.",
keywords = "PARK2, PINK1, autophagy, mitochondria, mitophagy, renal ischemia-reperfusion",
author = "Chengyuan Tang and Hailong Han and Mingjuan Yan and Shiyao Zhu and Jing Liu and Zhiwen Liu and Liyu He and Jieqiong Tan and Yu Liu and Hong Liu and Lin Sun and Shaobin Duan and Youming Peng and Fuyou Liu and Yin, {Xiao Ming} and Zhuohua Zhang and Zheng Dong",
note = "Funding Information: This study was supported inpart by grants from National Natural Science Foundation of China (81720108008, 81430017), and the National Institutes of Health and Department of Veterans Administration of USA. Funding Information: This work was supported by National Natural Science Foundation of China (NSFC) [grant number 81720108008]; HHS j NIH j National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [grant number 058831]; HHS j NIH j National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); [grant number 087843]; U.S. Department of Veterans Affairs (VA) [grant number 000319]; National Natural Science Foundation of China (NSFC) [grant number 81430017]; National Natural Science Foundation of China (NSFC) [grant number 81570622]. Funding Information: This work was supported by National Natural Science Foundation of China (NSFC) [grant number 81720108008]; HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [grant number 058831]; HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); [grant number 087843]; U.S. Department of Veterans Affairs (VA) [grant number 000319]; National Natural Science Foundation of China (NSFC) [grant number 81430017]; National Natural Science Foundation of China (NSFC) [grant number 81570622]. This study was supported inpart by grants from National Natural Science Foundation of China (81720108008, 81430017), and the National Institutes of Health and Department of Veterans Administration of USA. Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 Taylor & Francis.",
year = "2018",
month = may,
day = "4",
doi = "10.1080/15548627.2017.1405880",
language = "English (US)",
volume = "14",
pages = "880--897",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "5",
}