ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase

Russell RC, Tian Y, Yuan H, Park HW, Chang YY, Kim J, Kim H, Neufeld TP, Dillin A, Guan KL · 2013 · Nature Cell Biology · Atlas ID RUS2013

What this study shows

The authors asked how the ULK1 kinase switches on autophagy when amino acids are withdrawn. In mouse fibroblasts, amino-acid starvation raised the lipid-kinase activity of VPS34 complexes that contain ATG14L while lowering other VPS34 complexes, and the activation needed ULK kinase activity (lost in ULK-deficient and FIP200-null cells). ULK1 directly phosphorylated Beclin-1 at serine 14 (serine 15 in human), shown with purified kinase, mass spectrometry and a phospho-specific antibody; the mTOR inhibitor Torin1 or amino-acid withdrawal raised this phosphorylation only in cells with ULK activity. Cells reconstituted with non-phosphorylatable Beclin-1 S14A did not increase autophagosomes on amino-acid starvation, and the matching worm mutant (BEC-1 S6A) failed to fully rescue autophagic clearance in C. elegans embryos. The work provided evidence for a signalling chain from mTORC1 inhibition to ULK1, Beclin-1 and the ATG14L-VPS34 complex. Boundary: Mouse and human cell lines, in vitro kinase assays and C. elegans embryos; the mTOR step relies on Torin1 (which blocks mTORC1 and mTORC2) and amino-acid withdrawal. Not tested in mammalian tissues or in people.

Abstract

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Autophagy is the primary cellular catabolic program activated in response to nutrient starvation. Initiation of autophagy, particularly by amino-acid withdrawal, requires the ULK kinases. Despite its pivotal role in autophagy initiation, little is known about the mechanisms by which ULK promotes autophagy. Here we describe a molecular mechanism linking ULK to the pro-autophagic lipid kinase VPS34. Following amino-acid starvation or mTOR inhibition, the activated ULK1 phosphorylates Beclin-1 on Ser 14, thereby enhancing the activity of the ATG14L-containing VPS34 complexes.

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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: Wild-type, ULK-deficient (ULK1-/- with ULK2 knockdown) and FIP200-/- MEFs; HEK293 and HeLa Beclin-1 knockdown-reconstitution lines; in vitro kinase assays with insect-cell ULK1/ULK2; C. elegans bec-1 S6A transgenic embryos) 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	Wild-type, ULK-deficient (ULK1-/- with ULK2 knockdown) and FIP200-/- MEFs; HEK293 and HeLa Beclin-1 knockdown-reconstitution lines; in vitro kinase assays with insect-cell ULK1/ULK2; C. elegans bec-1 S6A transgenic embryos
Journal	Nature Cell Biology
Year	2013
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/ncb2757 · PMID 23685627 · Free full text (PMC3885611)

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	Amino-acid starvation or Torin1; genetic loss of ULK activity (ULK1-/- plus ULK2 knockdown, FIP200-/-); Beclin-1 S14A/S14D knock-down-reconstitution; C. elegans bec-1 S6A transgene
Target	ULK1 -> Beclin-1 Ser14 -> ATG14L-VPS34 complex
Model	Mouse and human cells; C. elegans
Effect	mTOR inhibition increased ULK1-dependent Beclin-1 S14 phosphorylation and ATG14L-VPS34 activity; blocking this phosphorylation reduced starvation-induced autophagy

In the Atlas

Links in the pathway map

Supports ULK1 activates Autophagy

Cite this paper

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Russell, R. C., Tian, Y., Yuan, H., Park, H. W., Chang, Y. Y., Kim, J., Kim, H., Neufeld, T. P., Dillin, A., & Guan, K. L. (2013). ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nature Cell Biology. https://doi.org/10.1038/ncb2757

@article{RUS2013,
  author       = {Russell, R. C. and Tian, Y. and Yuan, H. and Park, H. W. and Chang, Y. Y. and Kim, J. and Kim, H. and Neufeld, T. P. and Dillin, A. and Guan, K. L.},
  title        = {{ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase}},
  journal      = {Nature Cell Biology},
  year         = {2013},
  doi          = {10.1038/ncb2757},
  note         = {PMID: 23685627},
}

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 RUS2013) [Data set]. https://mtor-atlas.org/study/RUS2013/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_RUS2013,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record RUS2013},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/RUS2013/},
  doi          = {10.5281/zenodo.22059963}
}

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