Transcription factor Spalt-related (Salr) is a novel mTORC1 inhibitor in Drosophila activated by the integrated stress response, restricting anabolic growth and lipid storage during nutrient stress independently of AKT-FoxO signaling.
| Evidence tier | C Animal in vivo |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Drosophila melanogaster |
| Journal | The EMBO Journal |
| Year | 2026 |
| Peer reviewed | Yes |
| Source | DOI 10.1038/s44318-026-00858-1 · PMID 42436355 |
Anabolic and catabolic processes are coordinated by a conserved regulatory network including mTORC1 and FoxO. Spalt-related (Salr), previously implicated in organogenesis, is identified as a negative regulator of growth and lipid storage in Drosophila. Salr activates catabolic gene expression and restricts mTORC1-mediated cell growth in the fat body. Salr is activated in a slow and sustained manner through the integrated stress response, distinct from transient FoxO activation. Once activated, Salr counters nuclear localization of FoxO.
| Intervention | Integrated stress response activation (genetic) |
| Target | mTORC1 / Spalt-related (Salr) / FoxO |
| Model | Drosophila melanogaster |
| Effect | Inhibition of mTORC1-mediated cell growth; activation of catabolic gene expression; restriction of lipid storage |