ArticleJournal of neurology2022
Circulating cell-free mtDNA release is associated with the activation of cGAS-STING pathway and inflammation in mitochondrial diseases.
Article in Journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- Maternal hyperhomocysteinemia promotes adverse pregnancy outcomes via mtDNA-cGAS-STING signaling-mediated trophoblast mitophagy.Redox biology · 2026Article
- Mitochondrial Damage in Hemoglobinopathies: The Role of Cell-Free mtDNA as a Potential Biomarker.Biomedicines · 2026Article
- [Mechanisms of cGAS-STING-mediated chronic inflammation and targeted interventions in brain aging].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases.European journal of immunology · 2026Article
- Mitophagy-driven multidimensional regulation of tumor immune evasion and context-dependent therapeutic strategies.Journal of translational medicine · 2026Review
- Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction.Frontiers in immunology · 2026Review
- Role of the cGAS-STING signaling pathway in diabetes mellitus and its complications: from mechanisms to therapeutics.Frontiers in pharmacology · 2026Review
- Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- The "Mechano-Metabolic-Immune" crosstalk within the skeletal muscle microenvironment: evolution of homeostatic remodeling and quality control mechanisms.Frontiers in immunology · 2026Review
- cGAS-STING signaling in brain aging and neurodegeneration: molecular links and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Mitochondrial damage is associated with an early immune response in inclusion body myositis.Brain : a journal of neurology · 2025Article
- Inhibiting SSBP1 enhances ferroptosis and improves the effectiveness of sorafenib treatment for liver cancer.International journal of oncology · 2025Article
- cGAS-STING-NFκB PATHWAY PLAYS A ROLE IN BURN INJURY-INDUCED MUSCLE WASTING.Shock (Augusta, Ga.) · 2025Article
- Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS/STING pathway.Journal of pharmaceutical analysis · 2025Review
- Circulating mitochondrial DNA signature in cardiometabolic patients.Cardiovascular diabetology · 2025Article
- Elevated circulating cell-free mitochondrial DNA in fabry disease: insights into inflammatory activation.Frontiers in immunology · 2025Article
- Updates on the Role of Innate Immunity's Pattern Recognition Receptors in Vitiligo Pathogenesis and Therapeutic Potential.Clinical, cosmetic and investigational dermatology · 2025Review
- Elevated serum circulating cell-free mitochondrial DNA in amyotrophic lateral sclerosis.European journal of neurology · 2024Article
- Correlation between circulating cell-free mitochondrial DNA content and severity of knee degeneration in patients with knee osteoarthritis: a cross-sectional study.Arthritis research & therapy · 2024Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThere is increasing evidence for the role of inflammation in the pathogenesis of mitochondrial diseases (MDs). However, the mechanisms underlying mutation-induced inflammation in MD remain elusive. Our previous study suggested that mitophagy is impaired in the skeletal muscle of those with MD, likely causing mitochondrial DNA (mtDNA) release and thereby triggering inflammation. We here aimed to decipher the role of the cGAS-STING pathway in inflammatory process in MDs.
methodsWe investigated the levels of circulating cell-free mtDNA (ccf-mtDNA) in the serum of 104 patients with MDs. Immunofluorescence was performed in skeletal muscles in MDs and control. Biochemical analysis of muscle biopsies was conducted with western blot to detect cGAS, STING, TBK1, IRF3 and phosphorylated IRF3 (p-IRF3). RT-qPCR was performed to detect the downstream genes of type I interferon in skeletal muscles. Furthermore, a protein microarray was used to examine the cytokine levels in the serum of patients with MDs.
resultsWe found that ccf-mtDNA levels were significantly increased in those with MDs compared to the controls. Consistently, the immunofluorescent results showed that cytosolic dsDNA levels were increased in the muscle samples of MD patients. Biochemical analysis of muscle biopsies showed that cGAS, IRF3, and TBK1 protein levels were significantly increased in those with MDs, indicating that there was activation of the cGAS-STING pathway. RT-qPCR showed that downstream genes of type I interferon were upregulated in muscle samples of MDs. Protein microarray results showed that a total of six cytokines associated with the cGAS-STING pathway were significantly increased in MD patients (fold change > 1.2, p value < 0.05).
conclusionsThese findings suggest that increases in ccf-mtDNA levels is associated with the activation of the cGAS-STING pathway, thereby triggering inflammation in MDs.
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