ER-Lysosome Cholesterol Exchange Regulates Lysosomal Motility Through mTOR-Dependent LAMTOR1 Phosphorylation

Muthukottiappan P, Dehghani A, Muchamedin A, Ebner M, de Araujo MEG, Coman C, Rudnik S, Balachandran M, Fajardo-Callejon S, Akter F, Rösel N, …, Winter D · 2026 · bioRxiv (preprint) · Atlas ID MUT2026

What this study shows

Identifies a new layer of control over mTORC1's lysosomal machinery: cholesterol exchange between the ER and lysosome regulates lysosome movement via mTOR-dependent phosphorylation of LAMTOR1, a core component of the Ragulator complex that anchors the Rag GTPases already in this Atlas.

Abstract

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The subcellular distribution of lysosomes, the main degradative organelles of mammalian cells, responds to metabolic cues in a highly dynamic way. While lysosomal positioning due to amino acid levels is well-characterized, cholesterol-dependent regulation of lysosomal motility is incompletely understood. We explored impaired lysosomal cholesterol export using a mass spectrometry-based multi-OMICs approach, identifying widespread reallocation of resources and signaling pathway modulation.

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At a glance

Evidence type	PP Preprint, not peer-reviewed This is a preprint, not yet peer-reviewed -- treat its findings as provisional until formal publication. Preprints carry their own marker because peer-review status is a different question from which system was studied.
Study type	Preprint
Model system	Human cell lines
Journal	bioRxiv (preprint)
Year	2026
Peer reviewed	No
Record last updated	2026-10-01
Source	DOI 10.64898/2026.03.31.715514

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	Perturbation of lysosomal cholesterol export (multi-omics)
Target	mTOR / LAMTOR1 (Ragulator)
Model	Human cell lines
Effect	Cholesterol perturbation → mTOR-dependent LAMTOR1 (Ser56) phosphorylation controlling lysosomal motility

In the Atlas

Cite this paper

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Muthukottiappan, P., Dehghani, A., Muchamedin, A., Ebner, M., de Araujo, M. E. G., Coman, C., Rudnik, S., Balachandran, M., Fajardo-Callejon, S., Akter, F., Rösel, N., Saftig, P., Damme, M., Ahrends, R., Huber, L., Haucke, V., Gieselmann, V., & Winter, D. (2026). ER-Lysosome Cholesterol Exchange Regulates Lysosomal Motility Through mTOR-Dependent LAMTOR1 Phosphorylation. bioRxiv (preprint). https://doi.org/10.64898/2026.03.31.715514

@article{MUT2026,
  author       = {Muthukottiappan, P. and Dehghani, A. and Muchamedin, A. and Ebner, M. and de Araujo, M. E. G. and Coman, C. and Rudnik, S. and Balachandran, M. and Fajardo-Callejon, S. and Akter, F. and Rösel, N. and Saftig, P. and Damme, M. and Ahrends, R. and Huber, L. and Haucke, V. and Gieselmann, V. and Winter, D.},
  title        = {{ER-Lysosome Cholesterol Exchange Regulates Lysosomal Motility Through mTOR-Dependent LAMTOR1 Phosphorylation}},
  journal      = {bioRxiv (preprint)},
  year         = {2026},
  doi          = {10.64898/2026.03.31.715514},
}

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 MUT2026) [Data set]. https://mtor-atlas.org/study/MUT2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MUT2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MUT2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MUT2026/},
  doi          = {10.5281/zenodo.22059963}
}

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