{
  "abstract": "Sepsis, particularly septic shock, is a life-threatening condition driven by a dysregulated inflammatory response. Mitochondria are vital for orchestrating the LPS (lipopolysaccharide)-induced innate immune response. At the core of mitochondrial functionality lies mitochondrial RNA Polymerase (POLRMT). This study delineates POLRMT’s functional role and underlying mechanisms in LPS-induced pro-inflammatory responses across various macrophage models and in vivo. Through multiple genetic strategies, including stable shRNA-mediated knockdown and CRISPR/Cas9-mediated ablation, we demonstrated that POLRMT deficiency in THP-1 human macrophages, peripheral blood mononuclear cells (PBMCs), and murine bone marrow-derived macrophages (BMDMs) consistently attenuated LPS-induced transcriptional upregulation and secretion of key pro-inflammatory cytokines (IL-1β, TNF-α, IL-6). Conversely, POLRMT overexpression in THP-1 cells augmented these inflammatory responses. LPS-induced enhancements in mitochondrial Complex I activity and ATP content, alongside NFκB activation, were dependent on POLRMT expression. Genetic perturbation of POLRMT directly correlated with altered mitochondrial function and NFκB activity. Pharmacological inhibition of POLRMT with a specific inhibitor IMT1 also suppressed LPS-induced cytokine production, mitochondrial activation, and NFκB activity in vitro. The in vivo studies revealed that knockdown of POLRMT in CD68-expressing cells protected mice from LPS-induced septic shock, reducing mortality and systemic cytokine levels. Oral administration of IMT1 similarly conferred protection against septic shock, correlating with diminished circulating pro-inflammatory cytokines and reduced NFκB activity in murine PBMCs. Collectively, these findings establish POLRMT as a mediator of LPS-induced inflammatory responses in macrophages/monocytes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Emergency and Critical Care Medicine, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University",
    "Department of Emergency, Affiliated Hospital of Nanjing University of Chinese Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jie Qiong Ping"
    },
    {
      "affs": [
        1
      ],
      "name": "Tao Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Shi Wei Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Cheng Kong"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiang Yu Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Hong Peng Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9fjyq3dc0j1tq.bib",
  "cited_by": 0,
  "doi": "10.1186/s13062-026-00917-x",
  "fulltext_url": "https://doi.org/10.1186/s13062-026-00917-x",
  "id": "9fjyq3dc0j1tq",
  "issns": [
    "1745-6150"
  ],
  "landing_url": "https://doi.org/10.1186/s13062-026-00917-x",
  "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": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7171369395",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/9fjyq3dc0j1tq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:50Z",
      "native_id": "daf316bd8e6c4988a9e0daefb9c75778",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s13062-026-00917-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Sepsis Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Mitochondrial RNA polymerase is a critical mediator of LPS-induced inflammatory responses and septic shock",
  "title_text": "Mitochondrial RNA polymerase is a critical mediator of LPS-induced inflammatory responses and septic shock",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:50Z",
  "url": "https://research.draconitic.com/paper/9fjyq3dc0j1tq",
  "venue": "Biology Direct",
  "versions": []
}