Tryptophan Restores Recovery Competence Following Starvation in the Absence of Lysosomal Amino Acid Sensing

In Caenorhabditis elegans depd-5(lf) mutants, tryptophan supplementation restores recovery competence after starvation by countering unrestrained mTOR activity.

• Why it matters: Recovery from starvation requires coordinated nutrient sensing, but how amino acid availability restores post-starvation physiology when lysosomal sensing is impaired is unclear.
• What they did: A forward genetic screen identified depd-5 as a GATOR1 subunit; glucose refeeding reduced recovery competence in depd-5(lf), and amino acids—especially tryptophan—rescued it.
• The result: Raising tryptophan reduced catabolism via tdo-2 ablation and prolonged starvation restored recovery competence; raga-1(gf) mimicked and raga-1(lf) rescued, and a DEPDC5 mutation impaired starvation-induced mTOR inactivation in mammalian cells.