AMP-activated protein kinase; cellular energy sensor; inhibits mTORC1 under low-energy conditions.
| Tier | What it means | Studies |
|---|---|---|
| C | Animal in vivo | 2 |
| D | Mechanistic / in vitro / review | 6 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or mechanistic work.
| Study | Year | Tier | Finding |
|---|---|---|---|
| SONH2026 | 2026 | C | 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 l |
| ZHU2026 | 2026 | C | LKB1/AMPK deficiency exacerbates trichloroethylene-induced liver injury by impairing mTOR-regulated mitophagy and causing mitochondrial DNA leakage; rapamycin and AMPK activation are protective, estab |
| HOW2017 | 2017 | D | Pinned down HOW the diabetes drug metformin - a major longevity candidate - actually reaches mTOR. In the liver, metformin lowers cellular energy, and at low doses this shuts down mTORC1 specifically |
| KIM2011 | 2011 | D | 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 |
| LOF2011 | 2011 | D | ULK1 phosphorylates and inhibits AMPK in return, showing autophagy signaling is a bidirectional feedback loop, not a one-way switch. |
| GWI2008 | 2008 | D | Found a SECOND way the energy sensor AMPK shuts mTORC1 down. Besides acting through TSC2, AMPK directly phosphorylates Raptor - the core mTORC1 subunit - to halt growth when energy runs low. This 'met |
| INO2003 | 2003 | D | Established the energy-sensing arm of the pathway. When energy runs low, AMPK phosphorylates TSC2, boosting its ability to shut mTOR down - protecting the cell from burning through resources and from |
| ZHO2001 | 2001 | D | Metformin activates AMPK, suppressing hepatic gluconeogenesis and lipogenesis. |