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mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress

Grahammer, F. and Haenisch, N. and Steinhardt, F. and Sander, L. and Roerden, M. and Arnold, F. and Cordts, T. and Wanner, N. and Reichardt, W. and Kerjaschki, D. and Ruegg, M. A. and Hall, M. N. and Moulin, P. and Busch, H. and Boerries, M. and Walz, G. and Artunc, F. and Huber, T. B.. (2014) mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress. Proceedings of the National Academy of Sciences of the United States of America, 111 (27). E2817-E2826.

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Abstract

Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTORC1 inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By using constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells, and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in countercurrent multiplication and urine concentration. Although mTORC2 partially compensated for the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice and caused pronounced apoptosis, diminished proliferation rates, and delayed recovery. These findings identify mTORC1 as an important regulator of tubular energy metabolism and as a crucial component of ischemic stress responses.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Hall, Michael N. and Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
e-ISSN:1091-6490
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:12 Apr 2019 14:29
Deposited On:10 Oct 2014 09:19

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