Spatial and functional separation of mTORC1 signalling in response to different amino acid sources

Fernandes SA, Angelidaki DD, Nüchel J, Pan J, Gollwitzer P, Elkis Y, Artoni F, Wilhelm S, Kovacevic-Sarmiento M, Demetriades C · 2024 · Nature Cell Biology · Atlas ID FER2024

What this study shows

mTORC1 regulation and downstream substrate phosphorylation are spatially separated: lysosomal mTORC1 (fed by local lysosomal proteolysis) and cytoplasmic mTORC1 (fed by exogenous amino acids) phosphorylate distinct substrates depending on amino acid source, challenging the single lysosomal-hub model.

Abstract

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Amino acid (AA) availability is a robust determinant of cell growth through controlling mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity. According to the predominant model in the field, AA sufficiency drives the recruitment and activation of mTORC1 on the lysosomal surface by the heterodimeric Rag GTPases, from where it coordinates the majority of cellular processes. Importantly, however, the teleonomy of the proposed lysosomal regulation of mTORC1 and where mTORC1 acts on its effector proteins remain enigmatic.

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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: Human cells (HEK293)) 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	Human cells (HEK293)
Journal	Nature Cell Biology
Year	2024
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1038/s41556-024-01523-7 · PMID 39385049

Cite this paper

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Fernandes, S. A., Angelidaki, D. D., Nüchel, J., Pan, J., Gollwitzer, P., Elkis, Y., Artoni, F., Wilhelm, S., Kovacevic-Sarmiento, M., & Demetriades, C. (2024). Spatial and functional separation of mTORC1 signalling in response to different amino acid sources. Nature Cell Biology. https://doi.org/10.1038/s41556-024-01523-7

@article{FER2024,
  author       = {Fernandes, S. A. and Angelidaki, D. D. and Nüchel, J. and Pan, J. and Gollwitzer, P. and Elkis, Y. and Artoni, F. and Wilhelm, S. and Kovacevic-Sarmiento, M. and Demetriades, C.},
  title        = {{Spatial and functional separation of mTORC1 signalling in response to different amino acid sources}},
  journal      = {Nature Cell Biology},
  year         = {2024},
  doi          = {10.1038/s41556-024-01523-7},
  note         = {PMID: 39385049},
}

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 FER2024) [Data set]. https://mtor-atlas.org/study/FER2024/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_FER2024,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record FER2024},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/FER2024/},
  doi          = {10.5281/zenodo.22059963}
}