Regulation of TFEB and V-ATPases by mTORC1

Peña-Llopis S, Vega-Rubin-de-Celis S, Schwartz JC, Wolff NC, Tran TA, Zou L, Xie XJ, Corey DR, Brugarolas J · 2011 · EMBO Journal · Atlas ID PEN2011

What this study shows

Using Tsc2-null and wild-type mouse fibroblasts with and without rapamycin, the authors looked for genes whose expression follows mTORC1 activity and found 75 genes, enriched for subunits of the lysosomal proton pump (V-ATPase). mTORC1 also raised V-ATPase expression in mouse liver after Tsc1 deletion and in a prostate tumour model, through a transcriptional mechanism that needed the transcription factor TFEB: knocking down Tfeb cut the number of mTORC1-induced genes from 1146 to 424 probes, and about a quarter of mTORC1-induced genes depended on Tfeb. mTORC1 promoted albumin uptake (endocytosis) in a Tfeb- and V-ATPase-dependent way. In these serum-deprived cells, active mTORC1 (TSC loss) increased nuclear TFEB and rapamycin or Raptor knockdown reduced it, which is the opposite direction to the TFEB inhibition reported by later studies in fed or starved cells. Boundary: Mostly mouse and human cell lines under low serum; liver and prostate data are expression measurements. The direction of mTORC1 control over TFEB localisation here differs from later work and is condition-dependent.

Abstract

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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.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Tsc2-/- vs Tsc2+/+ immortalized MEFs (serum-deprived, +/- rapamycin) with microarrays; Tsc1 floxed primary MEFs and mouse liver (Ad-Cre); myr-Akt prostate model with everolimus (public data); HeLa cells with TSC2/Raptor knockdown) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Tsc2-/- vs Tsc2+/+ immortalized MEFs (serum-deprived, +/- rapamycin) with microarrays; Tsc1 floxed primary MEFs and mouse liver (Ad-Cre); myr-Akt prostate model with everolimus (public data); HeLa cells with TSC2/Raptor knockdown
Journal	EMBO Journal
Year	2011
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/emboj.2011.257 · PMID 21804531 · Free full text (PMC3160667)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Tsc2 or Tsc1 loss (genetic), rapamycin, Raptor knockdown; Tfeb knockdown
Target	mTORC1 -> TFEB -> V-ATPase genes
Model	Mouse cells and mouse liver; human HeLa cells
Effect	mTORC1 activation increased V-ATPase and lysosomal gene expression and endocytosis in a TFEB-dependent way; under low serum it increased TFEB nuclear localisation

In the Atlas

Links in the pathway map

Supports TFEB activates Lysosomal biogenesis
Points the other way on mTORC1 inhibits TFEB

Cite this paper

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Peña-Llopis, S., Vega-Rubin-de-Celis, S., Schwartz, J. C., Wolff, N. C., Tran, T. A., Zou, L., Xie, X. J., Corey, D. R., & Brugarolas, J. (2011). Regulation of TFEB and V-ATPases by mTORC1. EMBO Journal. https://doi.org/10.1038/emboj.2011.257

@article{PEN2011,
  author       = {Peña-Llopis, S. and Vega-Rubin-de-Celis, S. and Schwartz, J. C. and Wolff, N. C. and Tran, T. A. and Zou, L. and Xie, X. J. and Corey, D. R. and Brugarolas, J.},
  title        = {{Regulation of TFEB and V-ATPases by mTORC1}},
  journal      = {EMBO Journal},
  year         = {2011},
  doi          = {10.1038/emboj.2011.257},
  note         = {PMID: 21804531},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record PEN2011) [Data set]. https://mtor-atlas.org/study/PEN2011/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_PEN2011,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record PEN2011},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/PEN2011/},
  doi          = {10.5281/zenodo.22059963}
}

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