{
  "abstract": "Progressive hepatic fibrosis is the principal determinant of morbidity and mortality in metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD/MASH). Mitochondrial dysfunction is a hallmark of MASH, and the release of mitochondrial damage-associated molecular patterns (mito-DAMPs) from injured hepatocytes can promote fibrosis. However, how mitochondrial dynamics and quality control shape the fibrotic response in MASLD/MASH remains unclear. Here, through large-scale genomic analyses of mitochondrial genes governing mitophagy, fusion and fission in human MASLD, with a power-equivalent sample size of approximately 700,000 individuals, we identify a strong association between hepatic fibrosis and the mitochondrial fusion factor dynamin-like GTPase optic atrophy 1 (OPA1). OPA1 transcripts and protein abundance in the liver epithelium were progressively dysregulated with advancing fibrosis. In mice, hepatocyte-specific OPA1 loss alone was sufficient to induce hepatic stellate cell activation and fibrosis in zone 3, promoted the release of mito-DAMPs into the circulation and exacerbated fibrosis in experimental MASH. These findings identify OPA1 as a central regulator of the hepatic fibrotic response and connect defective mitochondrial homeostasis to mito-DAMP release, hepatic stellate cell activation and fibrosis in MASLD.",
  "abstract_shown": true,
  "affiliations": [
    "Beth Israel Deaconess Medical Center, Harvard Medical School"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "X. Yu"
    },
    {
      "name": "P. Huang"
    },
    {
      "name": "A. Justice"
    },
    {
      "name": "A. Hakim"
    },
    {
      "name": "Y. Nanki"
    },
    {
      "name": "Z. Abilov"
    },
    {
      "name": "E. B. O'Neill"
    },
    {
      "name": "J. Cruz Rodriguez"
    },
    {
      "name": "E. Cabrera"
    },
    {
      "name": "M. Sagatelian"
    },
    {
      "name": "C. S. Shankar"
    },
    {
      "name": "B. R. Flam"
    },
    {
      "name": "K. Al Khalloufi"
    },
    {
      "name": "H. Sesaki"
    },
    {
      "name": "S. Rong"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. V. Popov"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3tgzf9bv17b06.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.753666",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753666v1.full",
  "id": "3tgzf9bv17b06",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753666v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "2713|Liver Disease Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7214546234",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753666v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3tgzf9bv17b06.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:43Z",
      "native_id": "10.64898/2026.09.24.753666",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753666v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD",
  "title_text": "OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:43Z",
  "url": "https://research.draconitic.com/paper/3tgzf9bv17b06",
  "venue": "bioRxiv",
  "versions": []
}