1. Academic Validation
  2. Pannexin 1 targets mitophagy to mediate renal ischemia/reperfusion injury

Pannexin 1 targets mitophagy to mediate renal ischemia/reperfusion injury

  • Commun Biol. 2023 Aug 29;6(1):889. doi: 10.1038/s42003-023-05226-x.
Lianjiu Su # 1 2 3 Jiahao Zhang # 4 Jing Wang # 4 5 Xiaozhan Wang # 4 5 Edward Cao 6 Chen Yang 4 Qihao Sun 6 Ramadoss Sivakumar 6 Zhiyong Peng 7 8 9
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. sulianjiu@whu.edu.cn.
  • 2 Clinical Research Center of Hubei Critical Care Medicine, Wuhan, China. sulianjiu@whu.edu.cn.
  • 3 Department of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. sulianjiu@whu.edu.cn.
  • 4 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
  • 5 Clinical Research Center of Hubei Critical Care Medicine, Wuhan, China.
  • 6 Department of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • 7 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. pengzy5@hotmail.com.
  • 8 Clinical Research Center of Hubei Critical Care Medicine, Wuhan, China. pengzy5@hotmail.com.
  • 9 Center of Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15206, USA. pengzy5@hotmail.com.
  • # Contributed equally.
Abstract

Renal ischemia/reperfusion (I/R) injury contributes to the development of acute kidney injury (AKI). Kidney is the second organ rich in mitochondrial content next to the heart. Mitochondrial damage substantially contributes for AKI development. Mitophagy eliminates damaged mitochondria from the cells to maintain a healthy mitochondrial population, which plays an important role in AKI. Pannexin 1 (PANX1) channel transmembrane proteins are known to drive inflammation and release of adenosine triphosphate (ATP) during I/R injury. However, the specific role of PANX1 on Mitophagy regulation in renal I/R injury remains elusive. In this study, we find that serum level of PANX1 is elevated in patients who developed AKI after cardiac surgery, and the level of PANX1 is positively correlated with serum creatinine and urea nitrogen levels. Using the mouse model of renal I/R injury in vivo and cell-based hypoxia/reoxygenation (H/R) model in vitro, we prove that genetic deletion of PANX1 mitigate the kidney tubular cell death, oxidative stress and mitochondrial damage after I/R injury through enhanced Mitophagy. Mechanistically, PANX1 disrupts Mitophagy by influencing ATP-P2Y-mTOR signal pathway. These observations provide evidence that PANX1 could be a potential biomarker for AKI and a therapeutic target to alleviate AKI caused by I/R injury.

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