ArticleInternational journal of biological sciences2025
SLC25A33-mediated mitochondrial DNA synthesis plays a critical role in the inflammatory response of M1 macrophages by contributing to mitochondrial ROS and VDAC oligomerization.
Article in International journal of biological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Nucleotide metabolic reprogramming: a "double-edged sword" in obesity-related inflammation-from metabolic adaptation to pathological imbalance.Journal of physiology and biochemistry · 2026Review
- Basophil Extracellular Traps in Immunity and Disease.Cancers · 2026Review
- Mitochondrial profiling across macrophage states reveals inhibition of IL-4/IL-13 reprogramming by the integrated stress response.Science advances · 2026Article
- Macrophage anti-bacterial activity is controlled by adenylate kinase 4-mediated mitochondrial DNA synthesis.The Journal of experimental medicine · 2026Article
- MSC-derived exosomes ameliorate systemic lupus erythematosus by reprogramming macrophage mitochondrial homeostasis via the CMPK2-cGAS-STING axis.Journal of nanobiotechnology · 2026Article
- AQP4-IgG-Induced Astrocyte-Derived Small Extracellular Vesicles Carrying Mitochondrial DNA Regulate the TLR9/MyD88/NF-κB Pathway to Drive Microglial Activation and Neuromyelitis Optica.Neurochemical research · 2026Article
- Anti-Inflammatory and Protective Role of tiRNA-Glu-TTC-003 in Pediatric Sepsis Via TREM2/TLR4 Signaling Modulation.Inflammation · 2026Article
- Nucleotide metabolism reprogramming in obesity-associated cardiovascular inflammation: a new perspective.Frontiers in immunology · 2026Review
- Nucleotide Metabolic Reprogramming in Sepsis: From Immune-Cell Fate to Organ Injury and Precision Therapeutics.Journal of inflammation research · 2026Review
- Mitochondrial dysfunction and the regulatory cell death crosstalk network in chronic obstructive pulmonary disease: from oxidative stress mechanisms to targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- Mitochondria-immunometabolism in sepsis-induced liver injury: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- SLC25 in intestinal inflammation: mechanisms, pathological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
M1 macrophage polarization is modulated by the release of mitochondrial DNA (mtDNA) and induces the inflammatory immune response, which is further increased by the generation of mitochondrial reactive oxygen species (mtROS). The pyrimidine nucleotide carrier SLC25A33 is located in the mitochondrial inner membrane and is linked to mtDNA synthesis, but its role in the M1 macrophage inflammatory immune response remains unclear. Here, we elucidate the regulatory mechanisms responsible for upregulation of SLC25A33 expression during M1 macrophage polarization, SLC25A33-mediated mtROS production, and the inflammatory response. SLC25A33 expression was significantly elevated in CD14+ monocytes derived from patients with sepsis and LPS/interferon-gamma (IFN-γ)-stimulated peritoneal macrophages (PMs). SLC25A33 was upregulated by ATF4 through the MyD88-PI3K-mTORC1 pathway in LPS/IFN-γ-stimulated PMs. Furthermore, SLC25A33 increased mtDNA synthesis and the release of mtDNA into the cytosol, which was facilitated by mtROS-mediated voltage-dependent anion channel (VDAC) oligomer formation, thereby contributing to activation of the cGAS-STING inflammatory pathway. Conversely,
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