Branched-chain essential amino acid and the best-characterised nutrient input to mTORC1. Free leucine binds Sestrin2, releasing the GATOR2 brake; a competing model has leucyl-tRNA synthetase as the sensor instead.
| Tier | What it means | Studies |
|---|---|---|
| D | Mechanistic / in vitro / review | 5 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or mechanistic work.
| Study | Year | Tier | Finding |
|---|---|---|---|
| WYA2017 | 2017 | D | SLC38A9 effluxes essential amino acids (e.g. leucine) from lysosomes to activate mTORC1. |
| JEW2015 | 2015 | D | Glutamine activates mTORC1 via a Rag-independent, Arf1-dependent route distinct from leucine. |
| SAX2015 | 2015 | D | Solves the crystal structure of Sestrin2 bound to leucine, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor. |
| WOL2015 | 2015 | D | Sestrin2 is a direct leucine sensor whose leucine binding releases GATOR2 to activate mTORC1. |
| HAN2012 | 2012 | D | Leucyl-tRNA synthetase acts as an intracellular leucine sensor activating mTORC1 via the Rag pathway. |