{
  "abstract": "Imiquimod (IMQ) is a clinically approved drug widely used to treat skin malignancies; however, its application frequently provokes severe inflammation through NLRP3 inflammasome activation. The mechanism underlying IMQ-induced activation of the NLRP3 inflammasome is not completely defined. While IMQ-induced inhibition of mitochondrial electron transport chain complex I is necessary for activation of the NLRP3 inflammasome, it is not sufficient; suggesting presence of additional targets/triggers. The role of mitochondrial reactive oxygen species (mtROS) as the additional trigger to activate the inflammasome remains contentious based on conflicting reports. Using a unique genetic model lacking expression of mitochondrial membrane protein TMEM11 we reaffirm the role of mtROS in IMQ-induced NLRP3 inflammasome activation. Macrophages deficient in Tmem11, a mitochondrial contact site and cristae organizing system (MICOS)-associated membrane-protein, exhibit ultrastructural defects in cristae morphology without altering mitochondrial mass or mtDNA copy number. Loss of TMEM11 influences cristae length and density, reducing mitochondrial oxygen consumption. Tmem11-deficient macrophages exhibit normal NLRP3 inflammasome activation in response to canonical agonists (e.g., ATP, nigericin) but show caspase-1 hyperactivation and exaggerated IL-1{beta} and IL-18 secretion upon IMQ treatment. This exaggerated response is rescued by antioxidant treatment, confirming the role for mtROS. These findings demonstrate that cristae architecture restrains drug-induced mtROS to limit NLRP3 activation and that mtROS is a primary driver of IMQ-mediated NLRP3 inflammasome activation.",
  "abstract_shown": true,
  "affiliations": [
    "UCLA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "S. Srikanth"
    },
    {
      "name": "B. Wu"
    },
    {
      "name": "M. Do"
    },
    {
      "name": "C. Beninca"
    },
    {
      "name": "V. ARumugaswami"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Gwack"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3wm489zcpd5gt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.06.764965",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764965v1.full",
  "id": "3wm489zcpd5gt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764965v1",
  "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",
      "immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764965v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3wm489zcpd5gt.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:28:02Z",
      "native_id": "10.64898/2026.11.06.764965",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764965v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "TMEM11-Dependent Cristae Architecture Restrains Imiquimod-Induced NLRP3 Inflammasome Activation via Mitochondrial ROS",
  "title_text": "TMEM11-Dependent Cristae Architecture Restrains Imiquimod-Induced NLRP3 Inflammasome Activation via Mitochondrial ROS",
  "type": "preprint",
  "updated_at": "2026-11-10T00:28:02Z",
  "url": "https://research.draconitic.com/paper/3wm489zcpd5gt",
  "venue": "bioRxiv",
  "versions": []
}