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

Muthukottiappan P, Winter D et al. · 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

ShowHide

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.

Read the full abstract →

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Evidence type	PP Preprint, not peer-reviewed This is a preprint, not yet peer-reviewed -- treat its findings as provisional until formal publication.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	2026-08-22
Source	DOI 10.64898/2026.03.31.715514

Extracted findings

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

ShowHide

Muthukottiappan, P., et al. (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 Winter, D. and others},
  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}
}