{
  "abstract": "Ionizing radiation (IR) elicits both cytotoxic and immunomodulatory effects, yet the precise link between mitochondrial remodeling and immunogenic cell death (ICD) remains elusive. Here, we report that IR triggers robust mitophagy in pancreatic cancer cells, marked by mitochondrial damage, Parkin/BNIP3 upregulation, and increased autophagic flux. In parallel, IR induces key hallmarks of ICD, including calreticulin exposure, HMGB1 translocation, and the release of ATP and IFN-β. Notably, genetic or pharmacological inhibition of mitophagy attenuated this immunogenic profile, whereas mitophagy induction amplified it. We further demonstrate that mitophagy triggers the cytosolic release of mitochondrial DNA (mtDNA) to activate immune signaling, which can be reversed by blocking mtDNA replication. In murine models, Parkin overexpression enhanced mitophagy and ICD marker expression, leading to reduced tumor burden and prolonged survival following irradiation. Collectively, our findings indicate that mtDNA leakage downstream of mitophagy links mitochondrial remodeling to radiation-induced ICD, suggesting that modulation of mitochondrial dynamics may represent a strategy to enhance both radiosensitivity and the immunogenic potential of radiotherapy in pancreatic cancer.",
  "abstract_shown": true,
  "affiliations": [
    "School of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, 225009 China",
    "Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, 730000 China",
    "Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225002 China",
    "School of Basic Medical Sciences & School of Public Health, Faculty of Medicine, Yangzhou University, Yangzhou, 225009 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chenghao Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanxian Ren",
      "orcid": "0000-0002-0433-613X"
    },
    {
      "affs": [
        2
      ],
      "name": "Yong Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Huaying Yu"
    },
    {
      "affs": [
        3
      ],
      "name": "Jintao Cui"
    },
    {
      "affs": [
        3
      ],
      "name": "Fei Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Jin Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Ao Sun"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Heng Zhou",
      "orcid": "0000-0002-1457-4166"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ygtpxtmt7rzg.bib",
  "cited_by": 0,
  "doi": "10.1038/s41420-026-03269-7",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710541/",
  "id": "5ygtpxtmt7rzg",
  "issns": [
    "2058-7716"
  ],
  "landing_url": "https://doi.org/10.1038/s41420-026-03269-7",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "lcc",
      "QH573-671"
    ],
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7171778464",
  "pdf_url": "https://www.nature.com/articles/s41420-026-03269-7_reference.pdf",
  "pmcid": "PMC13710541",
  "pmid": "42934237",
  "published": "2026-07-01",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/5ygtpxtmt7rzg.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:29Z",
      "native_id": "PMC13710541",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41420-026-03269-7"
    },
    {
      "first_seen": "2026-11-01T14:21:16Z",
      "native_id": "08c292675df744b18f359195f58b9196",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41420-026-03269-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Mitophagy-dependent mitochondrial DNA release links ionizing radiation to immunogenic cell death in pancreatic cancer",
  "title_text": "Mitophagy-dependent mitochondrial DNA release links ionizing radiation to immunogenic cell death in pancreatic cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T14:20:43Z",
  "url": "https://research.draconitic.com/paper/5ygtpxtmt7rzg",
  "venue": "Cell Death Discovery",
  "versions": []
}