{
  "abstract": "How organisms recover from starvation to nutrient-replete physiology remains poorly understood. In C. elegans, we previously observed that transcription factor hlh-30 or a combination of glucose and linoleic acid in its absence are essential for survival with refeeding following starvation, i.e. recovery competence. A forward genetic screen to evaluate mechanisms identified depd-5, which encodes a GATOR1 subunit, loss of which is expected to impair amino acid sensing with unrestrained raga-1 and mTOR activation. Surprisingly, glucose refeeding reduced recovery competence in depd-5(lf, loss-of-function) animals, which was rescued by amino acids, specifically tryptophan. Increasing tryptophan levels in depd-5(lf) worms through supplementation, reduced tryptophan catabolism with tdo-2 ablation and prolonged starvation restored recovery competence. raga-1(gf, gain-of-function) recapitulated whereas raga-1(lf) rescued the impaired recovery competence in starved depd-5(lf) worms. An analogous DEPDC5 mutation in mammalian cells impaired starvation-induced mTOR inactivation. We conclude that tryptophan counters unrestrained mTOR activity to restore recovery competence following starvation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "John T. Murphy"
    },
    {
      "name": "Ryan Chang"
    },
    {
      "name": "Ziang Bi"
    },
    {
      "name": "Siana Kapoor"
    },
    {
      "name": "Haoying Zhang"
    },
    {
      "name": "David Seamons"
    },
    {
      "name": "Agastya Diwan"
    },
    {
      "name": "Micklaus Garcia"
    },
    {
      "name": "Moydul Islam"
    },
    {
      "name": "Kenji Rowel Q. Lim"
    },
    {
      "name": "Daniel L. Schneider"
    },
    {
      "name": "Brian M. Egan"
    },
    {
      "name": "David Rawnsley"
    },
    {
      "name": "Xiucui Ma"
    },
    {
      "name": "Kerry Kornfeld"
    },
    {
      "name": "Abhinav Diwan",
      "orcid": "0000-0001-7554-4772"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8m825vtqvgw9y.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.762351",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762351v1.full",
  "id": "8m825vtqvgw9y",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762351v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|PI3K/AKT/mTOR signaling in cancer"
    ]
  ],
  "openalex": "W7224082232",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762351v1.full.pdf",
  "pmcid": "PMC13734015",
  "pmid": "42990517",
  "published": "2026-10-27",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/8m825vtqvgw9y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:11Z",
      "native_id": "10.64898/2026.10.27.762351",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762351v1"
    },
    {
      "first_seen": "2026-11-08T12:23:40Z",
      "native_id": "PMC13734015",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.27.762351"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Tryptophan Restores Recovery Competence Following Starvation in the Absence of Lysosomal Amino Acid Sensing",
  "title_text": "Tryptophan Restores Recovery Competence Following Starvation in the Absence of Lysosomal Amino Acid Sensing",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:40Z",
  "url": "https://research.draconitic.com/paper/8m825vtqvgw9y",
  "venue": "bioRxiv",
  "versions": []
}