Pathway link ULK1-AUTOPHAGY
ULK1 Autophagy
ULK1 activates Autophagy.
Freed ULK1 kicks off autophagy – the cell's recycling programme, and the leading idea for why blocking this pathway might be beneficial.
The conditions it holds under
Mammalian cell studies (GAN2009, HOS2009, EGA2010). Autophagosome initiation is shown in cultured cells. Whether autophagy carries the benefits of mTOR inhibition in whole animals is not tested by these sources.
LC3-II accumulation, the standard readout for this step, marks autophagosome number, not flux: it rises whether autophagosomes are being made faster or degraded slower (e.g. under lysosomal/fusion block), so it cannot alone distinguish increased autophagy from stalled autophagy. A flux assay (e.g. LC3-II with and without a degradation blocker, or p62 turnover) is needed to tell the two apart.
- Time it takes
- minutes
- Step
- direct (one molecule acts on the other)
- Measured in
- mammalian cells
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2009 | M | ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagyGAN2009 The ULK1-ATG13-FIP200 complex transmits mTOR signalling to initiate autophagy. |
| 2009 | M | Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagyHOS2009 Showed the DIRECT brake mTORC1 uses on autophagy: when nutrients are plentiful, mTORC1 physically joins the ULK1-Atg13-FIP200 complex (the autophagy-starter kinase) and phosphorylates ULK1 to keep it off. Starvation or rapamycin releases this brake and autophagy begins. |
| 2010 | M | Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagyEGA2010 AMPK directly phosphorylates ULK1 to connect energy sensing to autophagy/mitophagy, opposing mTOR. |
| 2007 | M | siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagyCHA2007 The authors screened a kinase-targeted siRNA library in human HEK293 cells, using lipidation of the autophagy marker GFP-LC3 after amino-acid starvation as the readout. ULK1 came out of the screen: knocking it down blocked starvation-induced autophagy, while knocking down the related kinase ULK2 did not. ULK1 knockdown also blocked autophagy induced by rapamycin, which fits ULK1 acting downstream of mTOR. Overexpressed ULK1 inhibited autophagy independently of its kinase activity, and the dominant-negative effect mapped to residues 1-351, while the conserved C-terminal domain was needed for ULK1 to reach cytoplasmic structures, some of them LC3-positive. One of the early papers to place ULK1 as a required kinase for starvation-induced autophagy in mammalian cells. Boundary: Cultured human cell lines with siRNA and overexpression; no whole-animal data. The link to mTOR rests on rapamycin-induced autophagy, not on a measurement of mTORC1 acting on ULK1. Drafted from the abstract only (no PMC full text). |
| 2013 | M | ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinaseRUS2013 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. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
← The whole pathway · This link as JSON
Thank you. Your answer was counted anonymously.
Thank you. That helps us know which pages have been read by someone who knows the work.
Thank you. We will check it and correct the page.