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

Autophagy. 2012 May 1;8(5):826-37. doi: 10.4161/auto.19419. Epub 2012 May 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Aging / pathology*
  • Animals
  • Autophagy*
  • Autophagy-Related Protein 5
  • Biomarkers / metabolism
  • Creatinine / blood
  • Embryo, Mammalian / abnormalities
  • Embryo, Mammalian / pathology
  • Gene Deletion
  • Gene Knockout Techniques
  • Heat-Shock Proteins / metabolism
  • Kidney Tubules / abnormalities
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology*
  • Kidney Tubules / ultrastructure
  • Mice
  • Microtubule-Associated Proteins / deficiency
  • Microtubule-Associated Proteins / metabolism
  • Organ Specificity
  • Oxidative Stress
  • Reperfusion Injury / blood
  • Reperfusion Injury / pathology*
  • Sequestosome-1 Protein
  • Time Factors


  • Adaptor Proteins, Signal Transducing
  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Biomarkers
  • Heat-Shock Proteins
  • Microtubule-Associated Proteins
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse
  • Creatinine