PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury

Chengyuan Tang, Hailong Han, Mingjuan Yan, Shiyao Zhu, Jing Liu, Zhiwen Liu, Liyu He, Jieqiong Tan, Yu Liu, Hong Liu, Lin Sun, Shaobin Duan, Youming Peng, Fuyou Liu, Xiao Ming Yin, Zhuohua Zhang, Zheng Dong

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43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)880-897
Number of pages18
JournalAutophagy
Volume14
Issue number5
DOIs
StatePublished - May 4 2018

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Keywords

  • PARK2
  • PINK1
  • autophagy
  • mitochondria
  • mitophagy
  • renal ischemia-reperfusion

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Tang, C., Han, H., Yan, M., Zhu, S., Liu, J., Liu, Z., He, L., Tan, J., Liu, Y., Liu, H., Sun, L., Duan, S., Peng, Y., Liu, F., Yin, X. M., Zhang, Z., & Dong, Z. (2018). PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury. Autophagy, 14(5), 880-897. https://doi.org/10.1080/15548627.2017.1405880