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Abstract: TH-PO227

PINK1-Parkin Pathway of Mitophagy Is Activated to Protect against Renal Ischemia/Reperfusion Injury

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic


  • Tang, Chengyuan, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
  • Liu, Fuyou, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
  • Dong, Zheng, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China

Mitochondrial damage contributes to the pathogenesis of acute and chronic kidney diseases. 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. A major mitophagy pathway in mammalian cells is mediated by PINK1 and Parkin. 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. In this study, we examined PINK1- and Parkin- mediated mitophagy in the acute kidney injury (AKI) model of renal ischemia-reperfusion.


PINK1 and Parkin single or double knockout mice were compared to their matched wild-type mice for the response to 30 minutes of bilateral renal ischemia followed by 48 hours of reperfusion. Renal function, histopathology, biochemical analysis and electron microscopy analysis were performed to evaluate the effect of PINK1 and Parkin deletion. In vitro, HK-2 cells were subjected to ATP depletion/repletion treatment with CCCP (mitochondrial uncoupler) to examine the effects of PINK1 and Parkin knockdown.


Mitophagy was induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI, as evidenced by: (1) increased autophagy flux, (2) decreased expression of mitochondrial membrane proteins TOM20 and TIM23, and (3) increased formation of mitophagosomes. Mitophagy under these conditions was abrogated by PINK1 and Parkin deficiency, supporting a critical role of the PINK1/Parkin pathway in tubular cell mitophagy. Moreover, ischemic AKI was deteriorated in PINK1 and Parkin single as well as double knockout mice, as indicated by aggravated functional or structural renal damage, and enhanced tubular cell death. Mechanistically, PINK1 and Parkin deficiency enhanced mitochondrial damage, ROS production, and inflammatory response.


These results indicate that PINK1/Parkin-mediated mitophagy plays an important role in mitochondrial quality control, tubular cell survival, and renal function during AKI.