Activation of a metabolic gene regulatory network downstream of mTOR complex 1

Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, …, Manning BD · 2010 · Molecular Cell · Atlas ID DUV2010

What this study shows

Used cells with constitutively active mTORC1 (TSC2 loss) and rapamycin to map what mTORC1 switches on besides protein synthesis. Gene expression and metabolite profiling showed that mTORC1 activation is enough to drive glycolysis, the oxidative pentose phosphate pathway and de novo lipid synthesis. This ran through a transcriptional program of HIF1alpha and SREBP1/2 target genes; SREBP1 and 2 were needed for proliferation downstream of mTORC1, and their activation required S6K1. Boundary: cultured cells, mostly mouse fibroblasts with genetic mTORC1 activation; tissue and human relevance not tested here.

Abstract

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Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis.

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-/- mouse embryonic fibroblasts and other cells with rapamycin; transcriptomics, metabolomics, RNAi) 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-/- mouse embryonic fibroblasts and other cells with rapamycin; transcriptomics, metabolomics, RNAi
Journal	Molecular Cell
Year	2010
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.molcel.2010.06.022 · PMID 20670887 · Free full text (PMC2946786)

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 loss (constitutive mTORC1); rapamycin; SREBP and S6K1 knockdown
Target	mTORC1 -> HIF1alpha, SREBP1/2 (via S6K1)
Model	Mouse embryonic fibroblasts and other cell lines
Effect	mTORC1 activates glycolysis, oxidative PPP and lipid synthesis via HIF1alpha and SREBP

In the Atlas

Links in the pathway map

Supports mTORC1 activates SREBP1 / SREBP2
Supports SREBP1 / SREBP2 activates Lipid synthesis
Supports mTORC1 activates HIF-1α

Cite this paper

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Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., Vander Heiden, M. G., MacKeigan, J. P., Finan, P. M., Clish, C. B., Murphy, L. O., & Manning, B. D. (2010). Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Molecular Cell. https://doi.org/10.1016/j.molcel.2010.06.022

@article{DUV2010,
  author       = {Düvel, K. and Yecies, J. L. and Menon, S. and Raman, P. and Lipovsky, A. I. and Souza, A. L. and Triantafellow, E. and Ma, Q. and Gorski, R. and Cleaver, S. and Vander Heiden, M. G. and MacKeigan, J. P. and Finan, P. M. and Clish, C. B. and Murphy, L. O. and Manning, B. D.},
  title        = {{Activation of a metabolic gene regulatory network downstream of mTOR complex 1}},
  journal      = {Molecular Cell},
  year         = {2010},
  doi          = {10.1016/j.molcel.2010.06.022},
  note         = {PMID: 20670887},
}

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 DUV2010) [Data set]. https://mtor-atlas.org/study/DUV2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_DUV2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record DUV2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/DUV2010/},
  doi          = {10.5281/zenodo.22059963}
}

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