{
  "abstract": "Through mitochondrial outer membrane permeabilization (MOMP), mitochondria are central to apoptosis. MOMP is pro-inflammatory, impacting diverse processes including anti-tumor immunity and cellular senescence. Despite this, how damaged mitochondria activate inflammation remains unclear. Recent studies have shown that following MOMP, mitochondria are extensively ubiquitinated activating pro-inflammatory NF-{kappa}B signaling. We identify the E3 ligase, RNF213, as essential for pro-inflammatory mitochondrial ubiquitination following MOMP. RNF213 has an established role in pro- inflammatory, cell-autonomous immunity to bacteria and other pathogens. We discover that RNF213 is required for mitochondrial M1-linked (linear) ubiquitination. Interestingly, this was found to be independent of the canonical M1-ubiquitin ligase complex LUBAC. RNF213 can directly catalyze M1-linked ubiquitination. By promoting mitochondrial M1-linked ubiquitination, RNF213 initiates the recruitment of the essential NF{kappa}B adaptor molecule, NEMO, and subsequently activates pro-inflammatory NF-{kappa}B signaling. Collectively, our findings highlight striking similarities between how cells detect damaged mitochondria and intracellular pathogens, leading to inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "University of Glasgow"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "name": "R. Heilig"
    },
    {
      "name": "H. Glover"
    },
    {
      "name": "C. Mellor"
    },
    {
      "name": "C. Cloix"
    },
    {
      "name": "M. McIlwraith"
    },
    {
      "name": "N. Paul"
    },
    {
      "name": "P. Thomason"
    },
    {
      "name": "B. Prasad"
    },
    {
      "name": "A. Ahmed"
    },
    {
      "name": "H. Dupuis"
    },
    {
      "name": "D. Dalseno"
    },
    {
      "name": "L. Smith"
    },
    {
      "name": "J. Hamilton"
    },
    {
      "name": "E. Hall-Younger"
    },
    {
      "name": "E. Vringer"
    },
    {
      "name": "L. Buetow"
    },
    {
      "name": "A. Roca-Portoles"
    },
    {
      "name": "A. Montes-Gomez"
    },
    {
      "name": "G. Clark"
    },
    {
      "name": "A. Black"
    },
    {
      "name": "S. Lilla"
    },
    {
      "name": "S. Zanivan"
    },
    {
      "name": "L. Carlin"
    },
    {
      "name": "V. Helgason"
    },
    {
      "name": "D. Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "S. W. Tait"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/84psnrchymty4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.752888",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1.full",
  "id": "84psnrchymty4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1",
  "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",
      "cell biology"
    ],
    [
      "openalex",
      "1306|NF-κB Signaling Pathways"
    ]
  ],
  "openalex": "W7214013385",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/84psnrchymty4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:59Z",
      "native_id": "10.64898/2026.09.21.752888",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.752888v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "RNF213 M1-ubiquitinates damaged mitochondria to activate pro-inflammatory NF-κB signaling",
  "title_text": "RNF213 M1-ubiquitinates damaged mitochondria to activate pro-inflammatory NF-κB signaling",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:59Z",
  "url": "https://research.draconitic.com/paper/84psnrchymty4",
  "venue": "bioRxiv",
  "versions": []
}