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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Mitochondrial DNA Abnormalities in Idiopathic Inflammatory Myopathies: Innate Immune Signaling and Therapeutic Prospects

  • Guanyuan Wang1,2,3
  • Yurui Wang1,3
  • Xinran Wang1,2,3
  • Karl J. A. McCullagh4
  • Aijing Liu1,3,5
5 affiliations
  1. 1Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
  2. 2Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Shijiazhuang 050017, China
  3. 3Hebei International Joint Research Center on Rheumatic Diseases, Shijiazhuang 050000, China
  4. 4Discipline of Physiology, School of Pharmacy & Medical Sciences, Human Biology Building, University of Galway, H91 W5P7 Galway, Ireland
  5. 5Hebei Research Center for Stem Cell Medical Translational Engineering, Shijiazhuang 050017, China
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Abstract

Mitochondrial DNA (mtDNA) encodes essential components of oxidative phosphorylation and can stimulate innate immunity when released from mitochondria. Its genetic and immunological functions provide a rationale for investigating mtDNA abnormalities in idiopathic inflammatory myopathies (IIMs), where muscle dysfunction and inflammation coexist. Large-scale deletions and depletion have been documented in inclusion body myositis and polymyositis with mitochondrial pathology, while dermatomyositis studies reveal regional depletion and oxidative modifications in distinct biological compartments. These findings raise the possibility that mtDNA abnormalities contribute to both impaired mitochondrial function and inflammatory signaling. This review integrates subtype-specific findings with mechanistic studies of mtDNA release, DNA sensing, and inflammasome activation in IIM-related and non-IIM systems. It evaluates the evidence for mtDNA-based biomarkers and therapies targeting mitochondrial injury or downstream inflammation. The reported clinical benefits do not establish mtDNA-specific therapeutic effects. Defining how mitochondrial genome abnormalities and inflammatory signaling interact within each subtype is a priority for biomarker validation and therapeutic research.

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Cite

BibTeXRIS
BibTeX
@article{wang2026mitochondrial,
  title = {{Mitochondrial DNA Abnormalities in Idiopathic Inflammatory Myopathies: Innate Immune Signaling and Therapeutic Prospects}},
  author = {Guanyuan Wang and Yurui Wang and Xinran Wang and Karl J. A. McCullagh and Aijing Liu},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219949},
  url = {https://www.mdpi.com/1422-0067/27/21/9949},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Mitochondrial DNA Abnormalities in Idiopathic Inflammatory Myopathies: Innate Immune Signaling and Therapeutic Prospects
AU  - Guanyuan Wang
AU  - Yurui Wang
AU  - Xinran Wang
AU  - Karl J. A. McCullagh
AU  - Aijing Liu
PY  - 2026
DA  - 2026/11/06
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219949
UR  - https://www.mdpi.com/1422-0067/27/21/9949
AB  - Mitochondrial DNA (mtDNA) encodes essential components of oxidative phosphorylation and can stimulate innate immunity when released from mitochondria. Its genetic and immunological functions provide a rationale for investigating mtDNA abnormalities in idiopathic inflammatory myopathies (IIMs), where muscle dysfunction and inflammation coexist. Large-scale deletions and depletion have been documented in inclusion body myositis and polymyositis with mitochondrial pathology, while dermatomyositis studies reveal regional depletion and oxidative modifications in distinct biological compartments. These findings raise the possibility that mtDNA abnormalities contribute to both impaired mitochondrial function and inflammatory signaling. This review integrates subtype-specific findings with mechanistic studies of mtDNA release, DNA sensing, and inflammasome activation in IIM-related and non-IIM systems. It evaluates the evidence for mtDNA-based biomarkers and therapies targeting mitochondrial injury or downstream inflammation. The reported clinical benefits do not establish mtDNA-specific therapeutic effects. Defining how mitochondrial genome abnormalities and inflammatory signaling interact within each subtype is a priority for biomarker validation and therapeutic research.
SN  - 1422-0067
ER  -