Falling ATP, glucose withdrawal and a range of other insults. They converge on mTORC1 through two routes: AMPK, and physical relocation of the TSC complex to the lysosome.
Running out of fuel.
AMP and ADP binding to the AMPK γ-subunit plus LKB1-dependent T172 phosphorylation; also covers glucose withdrawal sensed via aldolase/lysosomal AXIN–LKB1.
| Tier | What it means | Studies |
|---|---|---|
| D | Mechanistic / in vitro / review | 4 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or mechanistic work.
| Study | Year | Tier | Finding |
|---|---|---|---|
| DEM2016 | 2016 | D | Lysosomal recruitment of TSC2 is a universal response to cellular stress that inhibits mTORC1. |
| MEN2014 | 2014 | D | Spatial control of the TSC complex integrates insulin and nutrient inputs at the lysosome. |
| 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 |
| ZHO2001 | 2001 | D | Metformin activates AMPK, suppressing hepatic gluconeogenesis and lipogenesis. |