{
  "abstract": "Despite major advances in the genetic diagnosis of mitochondrial disorders, effective disease-modifying therapies remain scarce. Here, we identify ebselen (EBS) as a promising therapeutic candidate through a phenotypic drug screen in a yeast model of Barth syndrome, a cardiomyopathy caused by defective cardiolipin maturation. EBS improved oxidative phosphorylation-dependent growth across diverse fungal models of mitochondrial diseases, including defects in complex I, complex IV, mitochondrial DNA maintenance, mitochondrial translation, and ATP synthase. Therapeutic efficacy was further validated in patient-derived fibroblasts, iPSC-derived cardiomyocytes, and a cardiolipin-deficient mouse model. Mechanistically, EBS acts independently of its established antioxidant activity by engaging a conserved metabolic program that suppresses cytosolic translation while stimulating pyruvate dehydrogenase-dependent tricarboxylic acid cycle activity, thereby improving proteostasis and mitochondrial bioenergetic function. These effects are likely coordinated through lysosome-associated mTOR signaling, consistent with the localization of EBS to lysosomes and its colocalization with mTOR. Together, our findings identify a conserved mechanism for enhancing mitochondrial function and establish ebselen as a strong candidate for therapeutic repurposing in Barth syndrome and a broad spectrum of inherited mitochondrial disorders.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 41,
  "authors": [
    {
      "name": "Claire Almyre"
    },
    {
      "name": "Anne-Louise Cayer"
    },
    {
      "name": "Nolwenn Bounaix"
    },
    {
      "name": "Anaïs Hoarau"
    },
    {
      "name": "Marie-Alix Derieppe"
    },
    {
      "name": "Julie Martineau"
    },
    {
      "name": "Pierre Costet"
    },
    {
      "name": "Camille Charles"
    },
    {
      "name": "Mélody Dufossée"
    },
    {
      "name": "Cécile Duplaa"
    },
    {
      "name": "Jim Dompierre"
    },
    {
      "name": "Bénédicte Salin"
    },
    {
      "name": "Marc-Alexandre D’elia"
    },
    {
      "name": "Corinne Blancard"
    },
    {
      "name": "Aurélie Massoni-Laporte"
    },
    {
      "name": "Stéphane Claverol"
    },
    {
      "name": "Caroline Tokarski"
    },
    {
      "name": "Yaser Hashem"
    },
    {
      "name": "Alexandre Favereaux"
    },
    {
      "name": "Yeranuhi Hovhannisyan"
    },
    {
      "name": "Juliette Jouhet"
    },
    {
      "name": "Cyrille Guimaraes"
    },
    {
      "name": "Jean-François Dumas"
    },
    {
      "name": "Olivier Baris"
    },
    {
      "name": "Laetitia Dard"
    },
    {
      "name": "Jérémy Richard"
    },
    {
      "name": "Vanessa Bergeron"
    },
    {
      "name": "Naïg Gueguen"
    },
    {
      "name": "Valérie Desquiret-Dumas"
    },
    {
      "name": "Jordan Rivron"
    },
    {
      "name": "Douglas Strathdee"
    },
    {
      "name": "Carole Sellem"
    },
    {
      "name": "Nathalie Bonnefoy"
    },
    {
      "name": "Laurent Monassier"
    },
    {
      "name": "Estelle Ayme-Dietrich"
    },
    {
      "name": "Onnik Agbulut"
    },
    {
      "name": "Stéphane Azoulay"
    },
    {
      "name": "Jean-Paul Di Rago"
    },
    {
      "name": "Vincent Procaccio"
    },
    {
      "name": "François Godard"
    },
    {
      "name": "Déborah Tribouillard-Tanvier"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2tgbrtsnjz9xt.bib",
  "cited_by": 0,
  "doi": "10.1038/s44321-026-00518-1",
  "fulltext_url": null,
  "id": "2tgbrtsnjz9xt",
  "issns": [
    "1757-4676",
    "1757-4684"
  ],
  "landing_url": "https://hal.science/hal-05798812v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|Mitochondrial Function and Pathology"
    ]
  ],
  "openalex": "W7220413266",
  "pdf_url": "https://link.springer.com/content/pdf/10.1038/s44321-026-00518-1.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": "Wiley Open Access",
  "ris": "https://research.draconitic.com/paper/2tgbrtsnjz9xt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "hal-05798812",
      "source": "hal",
      "url": "https://hal.science/hal-05798812v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Mitochondrial Function and Pathology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Ebselen restores mitochondrial function through metabolic rewiring in Barth syndrome and related mitochondrial diseases",
  "title_text": "Ebselen restores mitochondrial function through metabolic rewiring in Barth syndrome and related mitochondrial diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:56Z",
  "url": "https://research.draconitic.com/paper/2tgbrtsnjz9xt",
  "venue": "EMBO Molecular Medicine",
  "versions": []
}