Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia-reperfusion injury

Shuya Liu, Björn Hartleben, Oliver Kretz, Thorsten Wiech, Peter Igarashi, Noboru Mizushima, Gerd Walz, Tobias B. Huber

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

Autophagy is responsible for the degradation of protein aggregates and damaged organelles. Several studies have reported increased autophagic activity in tubular cells after kidney injury. Here, we examine the role of tubular cell autophagy in vivo under both physiological conditions and stress using two different tubular-specific Atg5-knockout mouse models. While Atg5 deletion in distal tubule cells does not cause a significant alteration in kidney function, deleting Atg5 in both distal and proximal tubule cells results in impaired kidney function. Already under physiological conditions, Atg5-null tubule cells display a significant accumulation of p62 and oxidative stress markers. Strikingly, tubular cell Atg5-deficiency dramatically sensitizes the kidneys to ischemic injury, resulting in impaired kidney function, accumulation of damaged mitochondria as well as increased tubular cell apoptosis and proliferation, highlighting the critical role that autophagy plays in maintaining tubular cell integrity during stress conditions.

Original languageEnglish (US)
Pages (from-to)826-837
Number of pages12
JournalAutophagy
Volume8
Issue number5
DOIs
StatePublished - May 2012

Bibliographical note

Funding Information:
We thank Charlotte Meyer, Ann-Kathrin Fritz (Renal Division, University Hospital Freiburg), Sigrun Nestel (Department of Anatomy, Albert-Ludwigs-University Freiburg) and Evelyn Wätzig (Department of Pathology, University Hospital Freiburg) for excellent technical assistance. This study was supported by DFG (Deutsche Forschungsgemeinschaft) grant KFO 201 (to GW and T.B.H.), by the Excellence Initiative of the German Federal and State Governments EXC 294 (to T.B.H.) and GSC-4, Spemann Graduate School (to S.L. and T.B.H.) and BMBF GerontosysII—NephAge (031589GA) (to T.B.H.).

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Acute kidney injury
  • Atg5
  • Autophagy
  • Kidney tubule system
  • p62

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