A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB

Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, Erdin S, Huynh T, Ferron M, Karsenty G, Vellard MC, Facchinetti V, …, Ballabio A · 2012 · The EMBO journal · Atlas ID SET2012

What this study shows

A lysosome-to-nucleus mechanism uses mTOR-dependent TFEB phosphorylation to sense lysosomal state.

Abstract

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The lysosome plays a key role in cellular homeostasis by controlling both cellular clearance and energy production to respond to environmental cues. However, the mechanisms mediating lysosomal adaptation are largely unknown. Here, we show that the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane. When nutrients are present, phosphorylation of TFEB by mTORC1 inhibits TFEB activity.

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: Mammalian cells) 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	Mammalian cells
Journal	The EMBO journal
Year	2012
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/emboj.2012.32 · PMID 22343943 · Free full text (PMC3298007)

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	Genetic/pharmacologic (mTORC1/TFEB)
Target	mTORC1 / TFEB
Model	Mammalian cells
Effect	A lysosome-to-nucleus signalling mechanism via mTORC1-TFEB senses and regulates the lysosome

In the Atlas

Links in the pathway map

Supports mTORC1 inhibits TFEB
Supports TFEB activates Autophagy
Supports Lysosomal biogenesis activates Lysosome

Learn the biology

Want to understand the biology behind this study? → The Lysosome as a Signalling Platform

Cite this paper

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Settembre, C., Zoncu, R., Medina, D. L., Vetrini, F., Erdin, S., Erdin, S., Huynh, T., Ferron, M., Karsenty, G., Vellard, M. C., Facchinetti, V., Sabatini, D. M., & Ballabio, A. (2012). A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. The EMBO journal. https://doi.org/10.1038/emboj.2012.32

@article{SET2012,
  author       = {Settembre, C. and Zoncu, R. and Medina, D. L. and Vetrini, F. and Erdin, S. and Erdin, S. and Huynh, T. and Ferron, M. and Karsenty, G. and Vellard, M. C. and Facchinetti, V. and Sabatini, D. M. and Ballabio, A.},
  title        = {{A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB}},
  journal      = {The EMBO journal},
  year         = {2012},
  doi          = {10.1038/emboj.2012.32},
  note         = {PMID: 22343943},
}

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 SET2012) [Data set]. https://mtor-atlas.org/study/SET2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SET2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SET2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SET2012/},
  doi          = {10.5281/zenodo.22059963}
}

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