ArticleAntioxidants (Basel, Switzerland)2025
cGAS-STING-NF-κB Axis Mediates Rotenone-Induced NLRP3 Inflammasome Activation Through Mitochondrial DNA Release.
Article in Antioxidants (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- The Secretome Derived From Human Umbilical Cord Mesenchymal Stem Cells Improves Skin Photoaging by Enhancing Mitophagy to Inhibit the cGAS-STING Pathway.Aging cell · 2026Article
- The Role of Skeletal Muscle Mitochondria in NLRP3 Inflammasome Signaling.Biomolecules · 2026Review
- Dual-Pathway Astrocyte Failure in Parkinson's Disease: Therapeutic Targeting of Nrf2/TFEB Suppression and cGAS-STING/Ferroptosis Activation.Molecular neurobiology · 2026Review
- Mitochondrial Toxicology of Heavy Metals and Pesticides: Transport Systems, Mitochondrial Dysfunction and Permeability Transition.International journal of molecular sciences · 2026Review
- The Molecular Basis of Ocular Aging: Mechanisms, Pathologies, and Emerging Therapeutics.Investigative ophthalmology & visual science · 2026Review
- Reprogramming of the hepatic ubiquitin‑immune axis: A unifying mechanism in liver disease progression (Review).Molecular medicine reports · 2026Review
- Dietary Antioxidants and Redox Signaling in Cancer Prevention: Mechanistic Insights and Metabolic Inflammation.Nutrients · 2026Review
- Neuroprotective Effects of Molecular Hydrogen via Oxidative Stress and Neuroinflammation Regulation in a 5xFAD Mouse Model.Antioxidants (Basel, Switzerland) · 2026Article
- Cyclodextrins as Modulators of Regulated Cell Death: Implications for Immunometabolism and Therapeutic Innovation.Pharmaceutics · 2026Review
- Low hypoxia tolerance as a determinant of the proinflammatory phenotype: a trained immunity perspective.Frontiers in immunology · 2026Review
- Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction.Frontiers in immunology · 2026Review
- Skeletal muscle dysfunction induced by cancer immunotherapy: mechanistics insights and surgical implications.Frontiers in immunology · 2026Review
- Crosstalk between innate immune signaling pathways and integrated TLR, NLRP3 inflammasome, cGAS-STING, and NF-κB networks in sepsis.Frontiers in cell and developmental biology · 2026Review
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- The potential role of lily polysaccharide in mitigating radiation-induced pneumonitis via the gut-lung axis: a comprehensive review.Frontiers in pharmacology · 2026Review
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Authors and funding
4 authors.
Funding
Abstract
Rotenone, a classical inhibitor of mitochondrial complex I, disrupts electron transport and promotes the generation of reactive oxygen species (ROS), contributing to inflammation and cell death. However, the precise molecular mechanisms linking mitochondrial dysfunction to inflammatory signaling remain incompletely understood. In this study, we investigated the role of the cGAS-STING pathway in rotenone-induced NLRP3 inflammasome activation in PMA-differentiated THP-1 macrophages. Rotenone treatment activated the cGAS-STING axis, as evidenced by increased cGAS expression and the phosphorylation of STING and TBK1. This activation led to the nuclear translocation of NF-κB and the upregulation of NLRP3, promoting inflammasome priming and IL-1β secretion. Inhibition of STING using H-151 markedly suppressed NLRP3 expression, NF-κB activation, and IL-1β release. Similarly, cyclosporin A, an inhibitor of mitochondrial permeability transition pore opening, reduced mitochondrial ROS, cytosolic oxidized mitochondrial DNA, and downstream activation of the cGAS-STING pathway, thereby attenuating inflammasome activation. These findings demonstrate that rotenone activates the NLRP3 inflammasome via mitochondrial ROS-mediated release of mtDNA and subsequent activation of the cGAS-STING-NF-κB signaling axis in THP-1-derived macrophages.
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