AMPK
AMP-activated protein kinase; cellular energy sensor; inhibits mTORC1 under low-energy conditions.
The low-fuel sensor.
αβγ heterotrimer. Two independent arms onto mTORC1 plus a direct activating arm onto ULK1 – the reason energy stress switches growth off and recycling on in one move.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 2 |
| M | Molecular — cells, biochemistry, structure | 6 |
| R | Review — secondary literature, not a new result | 1 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | 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. |
| 2026 | A | LKB1/AMPK deficiency aggravates mitochondrial DNA leakage via mTOR-dependent mitophagy damage in liver injury sensitized by trichloroethylene. ZHU2026 LKB1/AMPK deficiency exacerbates trichloroethylene-induced liver injury by impairing mTOR-regulated mitophagy and causing mitochondrial DNA leakage; rapamycin and AMPK activation are protective, nominating the LKB1/AMPK/mTOR axis as a candidate therapeutic target in mice; no human data. |
| 2026 | R | Nutrient-sensing pathways in adult stem cells: Orchestrating homeostasis, aging, and disease XIA2026 Proposes an integrated framework in which mTOR, AMPK, sirtuins, and insulin/IGF-1 signaling jointly govern adult stem cell transitions between quiescence, activation, and differentiation; age-related dysregulation of this nutrient-sensing network drives stem cell exhaustion and tissue degeneration, and interventions (mTOR inhibitors, AMPK activators, NAD+ precursors, dietary strategies) can restore ASC function. |
| 2017 | M | Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex HOW2017 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 through AMPK and the TSC complex. Direct mechanistic bridge between a widely-used drug, energy sensing, and the mTOR pathway. |
| 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. |
| 2008 | M | AMPK phosphorylation of raptor mediates a metabolic checkpoint GWI2008 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 'metabolic checkpoint' is exactly the switch that drugs like metformin and exercise tap into. |
| 2003 | M | TSC2 mediates cellular energy response to control cell growth and survival INO2003 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 starvation-induced death. The founding paper for how mTOR reads the cell's fuel gauge (complements the Akt-TSC2 growth-factor arm). |
| 2001 | M | Role of AMP-activated protein kinase in mechanism of metformin action ZHO2001 Metformin activates AMPK, suppressing hepatic gluconeogenesis and lipogenesis. |