{
  "abstract": "Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis and progressive cartilage and bone destruction. Synovial macrophages are central coordinators of inflammatory signaling, stromal activation, and osteoclastogenesis, yet their pathogenic functions cannot be explained by extracellular cytokine networks alone. Increasing evidence indicates that macrophage activation is coupled to cell-intrinsic mitochondrial metabolic reprogramming. Within the hypoxic, nutrient-variable, and inflammatory RA synovium, macrophages undergo coordinated changes in glycolysis and oxidative phosphorylation, tricarboxylic acid cycle flux, mitochondrial reactive oxygen species production, fission-fusion dynamics, mitophagy, and mitochondrial DNA homeostasis. These alterations reshape bioenergetics while generating metabolites and organelle-derived danger signals that engage hypoxia-inducible factor 1α, nuclear factor-κB, the NOD-like receptor family pyrin domain-containing 3 inflammasome, and cyclic GMP-AMP synthase-stimulator of interferon genes signaling. The resulting metabolic-inflammatory circuits can stabilize pathogenic macrophage states and propagate inflammation to fibroblast-like synoviocytes, endothelial cells, and osteoclast-lineage cells. This review integrates current evidence on macrophage heterogeneity, mitochondrial remodeling, and intercellular signaling in RA. We further evaluate mitochondria-targeted antioxidants, metabolic modulation, restoration of mitochondrial quality control, inhibition of mitochondrial danger-signal sensing, and multistage nanodelivery. Particular emphasis is placed on evidence strength, macrophage-subset specificity, and the distinction between disease-driving abnormalities and compensatory adaptations. Finally, we outline the biomarkers, human-tissue validation, spatial multi-omics, and delivery strategies required to translate macrophage mitochondrial immunometabolism into precision therapy for RA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.",
    "Department of Massage, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, People's Republic of China.",
    "Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences - CRMH, Hong Kong SAR, 999077, People's Republic of China.",
    "Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.",
    "Orthopedic Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, People's Republic of China.",
    "Orthopedic Department, The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People's Republic of China."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jingjing Zhao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Fuwei Pan"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Guangshuai Nie"
    },
    {
      "affs": [
        4
      ],
      "name": "Fuzeng Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Wang"
    },
    {
      "affs": [
        5
      ],
      "name": "Chongtao Han"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9pr2nmgegd5g9.bib",
  "cited_by": 0,
  "doi": "10.2147/jir.s645321",
  "fulltext_url": "https://europepmc.org/articles/PMC13679597",
  "id": "9pr2nmgegd5g9",
  "issns": [
    "1178-7031"
  ],
  "landing_url": "https://europepmc.org/article/MED/42899200",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2745|Rheumatoid Arthritis Research and Therapies"
    ]
  ],
  "openalex": "W7221912348",
  "pdf_url": "https://europepmc.org/articles/PMC13679597?pdf=render",
  "pmcid": "PMC13679597",
  "pmid": "42899200",
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9pr2nmgegd5g9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42899200",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42899200"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Rheumatoid Arthritis Research and Therapies",
      "subfield": "general"
    }
  ],
  "title": "Mitochondrial Metabolic Reprogramming in Macrophages: A Key Driver of Rheumatoid Arthritis.",
  "title_text": "Mitochondrial Metabolic Reprogramming in Macrophages: A Key Driver of Rheumatoid Arthritis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/9pr2nmgegd5g9",
  "venue": "Journal of inflammation research",
  "versions": []
}