These authors contributed equally to this work
Regulation of TFEB and V-ATPases by mTORC1
Article first published online: 29 JUL 2011
Copyright © 2011 European Molecular Biology Organization
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.
The EMBO Journal
Volume 30, Issue 16, pages 3242–3258, August 17, 2011
How to Cite
Peña-Llopis, S., Vega-Rubin-de-Celis, S., Schwartz, J. C., Wolff, N. C., Tran, T. A. T., Zou, L., Xie, X.-J., Corey, D. R. and Brugarolas, J. (2011), Regulation of TFEB and V-ATPases by mTORC1. The EMBO Journal, 30: 3242–3258. doi: 10.1038/emboj.2011.257
There is a Have you seen? (August 2011) associated with this Article.
- Issue published online: 17 AUG 2011
- Article first published online: 29 JUL 2011
- Manuscript Accepted: 24 JUN 2011
- Manuscript Received: 21 DEC 2010
Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is an important, highly conserved, regulator of cell growth. Ancient among the signals that regulate mTORC1 are nutrients. Amino acids direct mTORC1 to the surface of the late endosome/lysosome, where mTORC1 becomes receptive to other inputs. However, the interplay between endosomes and mTORC1 is poorly understood. Here, we report the discovery of a network that links mTORC1 to a critical component of the late endosome/lysosome, the V-ATPase. In an unbiased screen, we found that mTORC1 regulated the expression of, among other lysosomal genes, the V-ATPases. mTORC1 regulates V-ATPase expression both in cells and in mice. V-ATPase regulation by mTORC1 involves a transcription factor translocated in renal cancer, TFEB. TFEB is required for the expression of a large subset of mTORC1 responsive genes. mTORC1 coordinately regulates TFEB phosphorylation and nuclear localization and in a manner dependent on both TFEB and V-ATPases, mTORC1 promotes endocytosis. These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.