NUFIP1 is a ribosome receptor for starvation-induced ribophagy

Wyant GA, Abu-Remaileh M, Frenkel EM, Laqtom NN, Dharamdasani V, Lewis CA, Chan SH, Heinze I, Ori A, Sabatini DM · 2018 · Science · Atlas ID WYA2018

What this study shows

The authors purified lysosomes from human cells and measured how their protein content changes when mTORC1 is switched off by nutrient starvation or by the mTOR inhibitor Torin1, defining 828 lysosome-associated proteins. One responder, NUFIP1 (with its partner ZNHIT3), moved from the nucleus to autophagosomes and lysosomes after mTORC1 inhibition, bound ribosomes from Torin1-treated cells, and bound LC3B directly through a motif lost in the W40A mutant. Without NUFIP1 or its LC3B-binding ability, starvation or Torin1 no longer depleted ribosomal proteins and rRNA, while bulk autophagy and ferritin degradation were unaffected. In cells lacking the GATOR1 subunit DEPDC5, where mTORC1 ignores amino-acid loss, starvation no longer depleted ribosomal proteins but Torin1 still did, which points to mTORC1 inhibition as the trigger. NUFIP1 loss reduced survival under starvation (rescued by nucleosides) and blunted mTORC1 reactivation after long arginine deprivation. Boundary: Human and mouse cell lines over hours of starvation; Torin1 inhibits both mTOR complexes. No tissue or whole-animal data.

Abstract

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The lysosome degrades and recycles macromolecules, signals to the master growth regulator mTORC1 [mechanistic target of rapamycin (mTOR) complex 1], and is associated with human disease. We performed quantitative proteomic analyses of rapidly isolated lysosomes and found that nutrient levels and mTOR dynamically modulate the lysosomal proteome. Upon mTORC1 inhibition, NUFIP1 (nuclear fragile X mental retardation-interacting protein 1) redistributes from the nucleus to autophagosomes and lysosomes.

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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: HEK-293T and other human/mouse cell lines (incl. 8988T); LysoIP lysosome proteomics; CRISPR knockouts of NUFIP1, ATG7, DEPDC5 (GATOR1); Torin1, amino-acid and glucose starvation; electron microscopy) 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	HEK-293T and other human/mouse cell lines (incl. 8988T); LysoIP lysosome proteomics; CRISPR knockouts of NUFIP1, ATG7, DEPDC5 (GATOR1); Torin1, amino-acid and glucose starvation; electron microscopy
Journal	Science
Year	2018
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.aar2663 · PMID 29700228 · Free full text (PMC6020066)

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	Torin1 or nutrient (amino-acid/glucose) starvation; CRISPR loss of NUFIP1, ATG7 or DEPDC5; NUFIP1 W40A (LC3B-binding) and NLS/NES mutants
Target	mTORC1 inhibition -> NUFIP1-ZNHIT3 -> LC3B -> ribosome autophagy (ribophagy)
Model	Human and mouse cell lines
Effect	mTORC1 inhibition triggered NUFIP1-dependent autophagic degradation of ribosomes, which supported starvation survival and later mTORC1 reactivation

In the Atlas

Cite this paper

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Wyant, G. A., Abu-Remaileh, M., Frenkel, E. M., Laqtom, N. N., Dharamdasani, V., Lewis, C. A., Chan, S. H., Heinze, I., Ori, A., & Sabatini, D. M. (2018). NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Science. https://doi.org/10.1126/science.aar2663

@article{WYA2018,
  author       = {Wyant, G. A. and Abu-Remaileh, M. and Frenkel, E. M. and Laqtom, N. N. and Dharamdasani, V. and Lewis, C. A. and Chan, S. H. and Heinze, I. and Ori, A. and Sabatini, D. M.},
  title        = {{NUFIP1 is a ribosome receptor for starvation-induced ribophagy}},
  journal      = {Science},
  year         = {2018},
  doi          = {10.1126/science.aar2663},
  note         = {PMID: 29700228},
}

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 WYA2018) [Data set]. https://mtor-atlas.org/study/WYA2018/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_WYA2018,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record WYA2018},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/WYA2018/},
  doi          = {10.5281/zenodo.22059963}
}

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