{
  "abstract": "The mitochondrial prohibitin (PHB) complex is essential for mitochondrial homeostasis, yet its depletion produces opposite effects on lifespan: shortening it in wild-type C. elegans but extending it in insulin/IGF-1 receptor daf-2 mutants, which show an attenuated mitochondrial unfolded protein response (UPRmt). To identify regulators of this differential stress response and its role in aging, we conducted the first genome-wide double-RNAi screen in C. elegans. We identify the ubiquitin-specific peptidase USP-48 as a modulator of the UPRmt, specially required for lifespan extension under reduced insulin signaling. USP-48 influences mitochondrial structure and function and cooperates with the transcription factor DVE-1 to regulate the UPRmt largely independent of activating transcription factor associated with stress-1 (ATFS-1). Tissue-specific analysis shows that USP-48 is required for lifespan primarily in the hypodermis, with a smaller germline contribution, but is dispensable in muscle and intestine. Mechanistically, USP-48 promotes histone H2B deubiquitination to shape stress-responsive transcription, revealing ubiquitination as a key determinant of metabolism-dependent longevity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Sergio Gordillo-García"
    },
    {
      "name": "Jesus Fernandez-Abascal"
    },
    {
      "name": "Blanca Hernando-Rodríguez"
    },
    {
      "name": "María Jesús Rodríguez-Palero"
    },
    {
      "name": "Laura Cantalejo-Carrasco"
    },
    {
      "name": "Aitor Jarit-Cabanillas"
    },
    {
      "name": "Manuel D. Martínez-Bueno"
    },
    {
      "name": "Mercedes M. Pérez-Jiménez"
    },
    {
      "name": "Enrique J. Clavijo-Bernal"
    },
    {
      "name": "Aitana Cambón"
    },
    {
      "name": "Ildefonso Cases"
    },
    {
      "name": "Matthias Eder"
    },
    {
      "name": "Marta Artal-Sanz",
      "orcid": "0000-0003-1126-0492"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/913ame586fyks.bib",
  "cited_by": 0,
  "doi": "10.1016/j.celrep.2026.118067",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714240/",
  "id": "913ame586fyks",
  "issns": [
    "2211-1247"
  ],
  "landing_url": "https://linkinghub.elsevier.com/retrieve/pii/S2211124726011460",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7214996082",
  "pdf_url": null,
  "pmcid": "PMC13714240",
  "pmid": "42814573",
  "published": "2026-09-30",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/913ame586fyks.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:34Z",
      "native_id": "10.1016/j.celrep.2026.118067",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2211124726011460"
    },
    {
      "first_seen": "2026-11-01T12:21:46Z",
      "native_id": "PMC13714240",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.celrep.2026.118067"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "USP-48 enables insulin-mediated longevity and modulates the mitochondrial stress response",
  "title_text": "USP-48 enables insulin-mediated longevity and modulates the mitochondrial stress response",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:46Z",
  "url": "https://research.draconitic.com/paper/913ame586fyks",
  "venue": "Cell Reports",
  "versions": []
}