Inhibition of MTOR disrupts autophagic flux in podocytes

Davide P. Cinà, Tuncer Onay, Aarti Paltoo, Chengjin Li, Yoshiro Maezawa, Javier De Arteaga, Andrea Jurisicova, Susan E. Quaggin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


Inhibitors of the mammalian target of rapamycin (MTOR) belong to a family of drugs with potent immunosuppressive, antiangiogenic, and antiproliferative properties. De novo or worsening proteinuria can occur during treatment with these agents, but the mechanism by which this occurs is unknown. We generated and characterized mice carrying a podocyte-selective knockout of the Mtor gene. Although Mtor was dispensable in developing podocytes, these mice developed proteinuria at 3 weeks and end stage renal failure by 5 weeks after birth. Podocytes from these mice exhibited an accumulation of the autophagosome marker LC3 (rat microtubule-associated protein 1 light chain 3), autophagosomes, autophagolysosomal vesicles, and damaged mitochondria. Similarly, human podocytes treated with the MTOR inhibitor rapamycin accumulated autophagosomes and autophagolysosomes. Taken together, these results suggest that disruption of the autophagic pathway may play a role in the pathogenesis of proteinuria in patients treated with MTOR inhibitors.

Original languageEnglish (US)
Pages (from-to)412-420
Number of pages9
JournalJournal of the American Society of Nephrology
Issue number3
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Nephrology


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