A gene network regulating lysosomal biogenesis and function

Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, …, Ballabio A · 2009 · Science · Atlas ID SAR2009

What this study shows

The authors found that most lysosomal genes show coordinated expression and share a promoter motif (later called the CLEAR element) that is bound and regulated by the transcription factor TFEB. Under conditions of abnormal lysosomal storage, TFEB moved from the cytoplasm to the nucleus and switched on its target genes. Overexpressing TFEB in cultured cells increased the number of lysosomes and the cells' capacity to degrade complex molecules, including glycosaminoglycans and the mutant huntingtin protein. The paper provided evidence that lysosome production is run by a transcriptional programme with TFEB at its centre, which later work tied to mTORC1 control. Boundary: Cultured cells with TFEB overexpression; mTOR was not studied in this paper. Therapeutic potential for storage and neurodegenerative disease is proposed, not tested. Drafted from the abstract only (no PMC full text).

Abstract

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Lysosomes are organelles central to degradation and recycling processes in animal cells. Whether lysosomal activity is coordinated to respond to cellular needs remains unclear. We found that most lysosomal genes exhibit coordinated transcriptional behavior and are regulated by the transcription factor EB (TFEB). Under aberrant lysosomal storage conditions, TFEB translocated from the cytoplasm to the nucleus, resulting in the activation of its target genes.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Promoter/expression analysis of lysosomal genes; cultured human (HeLa) and mouse cells with TFEB overexpression; lysosomal storage conditions (sucrose loading)) 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	Promoter/expression analysis of lysosomal genes; cultured human (HeLa) and mouse cells with TFEB overexpression; lysosomal storage conditions (sucrose loading)
Journal	Science
Year	2009
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.1174447 · PMID 19556463

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	TFEB overexpression; induction of lysosomal storage
Target	TFEB / CLEAR lysosomal gene network
Model	Human and mouse cultured cells
Effect	TFEB overexpression increased lysosomal gene expression, lysosome number and clearance of glycosaminoglycans and mutant huntingtin

In the Atlas

Links in the pathway map

Supports TFEB activates Lysosomal biogenesis

Cite this paper

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Sardiello, M., Palmieri, M., di Ronza, A., Medina, D. L., Valenza, M., Gennarino, V. A., Di Malta, C., Donaudy, F., Embrione, V., Polishchuk, R. S., Banfi, S., Parenti, G., Cattaneo, E., & Ballabio, A. (2009). A gene network regulating lysosomal biogenesis and function. Science. https://doi.org/10.1126/science.1174447

@article{SAR2009,
  author       = {Sardiello, M. and Palmieri, M. and di Ronza, A. and Medina, D. L. and Valenza, M. and Gennarino, V. A. and Di Malta, C. and Donaudy, F. and Embrione, V. and Polishchuk, R. S. and Banfi, S. and Parenti, G. and Cattaneo, E. and Ballabio, A.},
  title        = {{A gene network regulating lysosomal biogenesis and function}},
  journal      = {Science},
  year         = {2009},
  doi          = {10.1126/science.1174447},
  note         = {PMID: 19556463},
}

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 SAR2009) [Data set]. https://mtor-atlas.org/study/SAR2009/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SAR2009,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SAR2009},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SAR2009/},
  doi          = {10.5281/zenodo.22059963}
}

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