{
  "abstract": "Sepsis-associated organ dysfunction arises from immune dysregulation, heterogeneous microcirculatory perfusion, impaired oxygen utilization, and cellular metabolic disturbances. Hypoxia-inducible factor-1α (HIF-1α) links oxygen sensing and inflammatory signaling to substrate use and mitochondrial function, but its effects vary with cell type, organ energy demand, and disease stage. This review uses metabolic flexibility and organ-specific metabolic mismatch to integrate these differences. Metabolic flexibility denotes the capacity to adjust energy-producing pathways during stress and restore efficient oxidative metabolism after stress subsides; mismatch develops when cellular energy production no longer meets immediate organ function or repair requirements. HIF-1α-related glycolysis supports early antimicrobial responses in myeloid cells and short-term hypoxic tolerance in some parenchymal cells. Persistent glycolysis combined with restricted pyruvate and fatty acid oxidation and impaired mitochondrial renewal may instead prolong inflammation and limit barrier repair, tubular transport, myocardial contraction, hepatic clearance, and neurological recovery. Differences among the lungs, kidneys, heart, intestine, liver, and brain indicate that global HIF activation or inhibition is unlikely to produce uniform benefit. Cell type-resolved localization, dynamic metabolic flux, mitochondrial function, and organ-level endpoints are therefore required to distinguish adaptive reprogramming from persistent bioenergetic dysfunction and to guide phase-matched metabolic intervention.",
  "abstract_shown": true,
  "affiliations": [
    "Emergency Center, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China",
    "Department of Critical Care Medicine, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuge Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiantao Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yue Mo"
    },
    {
      "affs": [
        1
      ],
      "name": "Yaoqi Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoxi Yan"
    },
    {
      "affs": [
        1
      ],
      "name": "Caifen Yan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yingzhen Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1c600mhjd9qv0.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1998563",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13697615/",
  "id": "1c600mhjd9qv0",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://doi.org/10.3389/fimmu.2026.1998563",
  "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",
      "Review"
    ],
    [
      "openalex",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W7221535575",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13697615/pdf/?tool=EBI",
  "pmcid": "PMC13697615",
  "pmid": "42936448",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1c600mhjd9qv0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:38Z",
      "native_id": "PMC13697615",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1998563"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1998563",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1998563/full"
    },
    {
      "first_seen": "2026-10-30T12:21:25Z",
      "native_id": "PMC:PMC13697615",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13697615"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Hypoxia, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Hypoxia-inducible factor-1α–mediated metabolic reprogramming in sepsis-associated organ dysfunction: organ-specific metabolic mismatch and therapeutic perspectives",
  "title_text": "Hypoxia-inducible factor-1α–mediated metabolic reprogramming in sepsis-associated organ dysfunction: organ-specific metabolic mismatch and therapeutic perspectives",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:37Z",
  "url": "https://research.draconitic.com/paper/1c600mhjd9qv0",
  "venue": "Frontiers in Immunology",
  "versions": []
}