ULK1
Initiator of autophagy; target of mTORC1 inhibition and AMPK activation.
The switch that starts self-digestion.
mTORC1 phosphorylates S757 to block the AMPK–ULK1 interaction; ULK1 also feeds back to phosphorylate and dampen AMPK, making this a closed loop rather than a switch.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| H | Human study | 1 |
| A | Animal model | 1 |
| M | Molecular — cells, biochemistry, structure | 3 |
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | H | Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study GIL2026 Low-dose rapamycin in ME/CFS patients reduced fatigue symptoms, modulated purine biosynthesis via IMP dehydrogenase inhibition, reduced microglial inflammatory responses, and improved mitochondrial energy metabolism in a phase-II observational pilot study. |
| 2026 | A | Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF SONH2026 Urolithin A ameliorates HFpEF cardiac remodeling in mice by activating AMPK and inhibiting mTOR to restore mitophagic flux, while simultaneously remodeling the gut microbiome-ceramide axis to reduce lipotoxic stress. |
| 2011 | M | Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop LOF2011 ULK1 phosphorylates and inhibits AMPK in return, showing autophagy signaling is a bidirectional feedback loop, not a one-way switch. |
| 2011 | M | AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 KIM2011 Revealed the tug-of-war over ULK1: the energy sensor AMPK phosphorylates ULK1 at activating sites to turn autophagy ON when energy is low, while mTORC1 phosphorylates a different site (Ser757) to keep it OFF and even blocks AMPK from reaching ULK1. Two opposing kinases wired to the same switch. |
| 2009 | M | Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy HOS2009 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. |