ArticleImmunity2022
Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling.
Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 471 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
471 citing papers in PubMed, 672 citations in OpenAlex.
- A nucleic acid regulation strategy under mechanical stress for intervertebral disc degeneration treatment.Bioactive materials · 2026Article
- Insights from integrative spatial transcriptomics in sepsis-associated acute kidney injury.Nature reviews. Nephrology · 2026Review
- Oxidized mitochondrial DNA as a potential biomarker and mechanistic driver of autophagy-mitophagy dysregulation in pulmonary arterial hypertension: a narrative review.Molecular biology reports · 2026Review
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration.Neural regeneration research · 2026Article
- Exercise promotes host anti-infection activity through CNDP2 metabolite-mediated inflammasome hyperactivation.PLoS pathogens · 2026Article
- From mitochondria to innate immunity: The mtDNA-driven cGAS/STING-NLRP3 cascade and its therapeutic implications in neurodegenerative diseases (Review).Experimental and therapeutic medicine · 2026Review
- Hexosamine Biosynthetic Pathway and Fatty Acid β-Oxidative Imbalance: A Key Mechanism by Which Abnormal Macrophage Lipophagy Promotes Atherosclerosis in Diabetes.Cardiovascular drugs and therapy · 2026Review
- TREM2 Attenuates Microglial Pyroptosis in Sepsis-Associated Encephalopathy Through Modulation of the mtDNA-cGAS-STING Pathway.Molecular neurobiology · 2026Article
- Ultrasound-Responsive Piezoelectric Fibrous Membrane Promotes Neurological Recovery After TBI by Modulating Microglial Polarization via Restoring Mitochondrial Dynamic Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The NLRP3 inflammasome in physiological and dysfunctional host response in human sepsis and critical illness: a narrative review.Critical care (London, England) · 2026Review
- Sonogenetics Nanomedicine Activates the cGAS-STING Pathway for Immunotherapy of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Basophil Extracellular Traps in Immunity and Disease.Cancers · 2026Review
- Mitochondrial Quality Control Links Exercise to Sterile Inflammation in the Cardiovascular System: A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
- Leptin attenuates heat stress-induced mitoxyperilysis in porcine Sertoli cells by suppressing the mtDNA-cGAS-STING axis.Journal of animal science and biotechnology · 2026Article
- NRF2 activation attenuates obesity-induced adipose inflammation by suppressing STING signaling, with depot-specific regulation.Journal of translational medicine · 2026Article
- The Oxidative-Mitochondrial-Inflammatory Axis in Retinitis Pigmentosa: Extracellular mtDNA as Biomarker and Therapeutic Read-Out.Antioxidants (Basel, Switzerland) · 2026Review
- Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.Neural regeneration research · 2026Article
- Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation.Journal of hematology & oncology · 2026Article
- Mitochondria as the Hub of Apoptosis: A Comprehensive Insight From Mitochondria to Interactions With Other Organelles.MedComm · 2026Review
411 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Mitochondrial DNA (mtDNA) escaping stressed mitochondria provokes inflammation via cGAS-STING pathway activation and, when oxidized (Ox-mtDNA), it binds cytosolic NLRP3, thereby triggering inflammasome activation. However, it is unknown how and in which form Ox-mtDNA exits stressed mitochondria in non-apoptotic macrophages. We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization. This occurred independently of mtDNA or reactive oxygen species, which induce Ox-mtDNA generation. Within mitochondria, Ox-mtDNA was either repaired by DNA glycosylase OGG1 or cleaved by the endonuclease FEN1 to 500-650 bp fragments that exited mitochondria via mPTP- and VDAC-dependent channels to initiate cytosolic NLRP3 inflammasome activation. Ox-mtDNA fragments also activated cGAS-STING signaling and gave rise to pro-inflammatory extracellular DNA. Understanding this process will advance the development of potential treatments for chronic inflammatory diseases, exemplified by FEN1 inhibitors that suppressed interleukin-1β (IL-1β) production and mtDNA release in mice.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.