ArticleNature cell biology2024
Mitochondrial DNA replication stress triggers a pro-inflammatory endosomal pathway of nucleoid disposal.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.Frontiers in immunology · 2026Pooled it
- A BAI1-PSTB-Hydrogel promotes diabetic wound healing by targeting mtDNA leakage and the cGAS-STING axis to alleviate endothelial senescence.Bioactive materials · 2026Article
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Mitochondrial Quality Control Links Exercise to Sterile Inflammation in the Cardiovascular System: A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
- Au(III) Complexes as Pyroptosis Inducers by Targeting Mitochondrial DNA for Tumor Immunity.Angewandte Chemie (International ed. in English) · 2026Article
- Herpes simplex virus 1 subverts the mitochondrial network to support the infection: A lesson on mitochondrial versatility.bioRxiv : the preprint server for biology · 2026Article
- ERCC6 at the Transcription-Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses.International journal of molecular sciences · 2026Review
- Cross-species transcriptomic integration reveals a MIRO1-mediated macrophage-T cell axis in glioma.Life science alliance · 2026Article
- Mitochondrial Dysfunction in Circulating Blood Cells and Biological Aging: A Review of Mechanisms and Evidence.Biomolecules · 2026Review
- The MIRO1-BAX Complex Dictates Life and Death at the Mitochondrial Gate.bioRxiv : the preprint server for biology · 2026Article
- From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Size-dependent ruthenium/ceria nanozymes synchronize catalytic ROS scavenging and electrostatic mtDNA sequestration for periodontitis therapy.Journal of nanobiotechnology · 2026Article
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis.Precision clinical medicine · 2026Review
- Chrysin Attenuates Dry Eye Progression by Suppressing NOX2-Dependent Ferroptosis and STING/NLRP3-Mediated Inflammatory Responses.Investigative ophthalmology & visual science · 2026Article
- Mitochondrial drivers of stem cell aging and inflammaging.npj aging · 2026Review
- [Research progress on the mechanism of mitochondrial dynamics in diabetic foot ulcers and its related intervention strategies].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Review
- Mechano-metabolic feedback connects tissue fluidity to mitochondrial DNA-dependent immunity in breast cancer.Nature communications · 2026Article
- Interferon-alpha selectively signals mitochondrial pore opening to allow mitochondrial RNA release in systemic lupus erythematosus: pathophysiological implications.Cell communication and signaling : CCS · 2026Article
- Membranes arrest the coarsening of mitochondrial condensates in human cells.Communications biology · 2026Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Mitochondrial DNA (mtDNA) encodes essential subunits of the oxidative phosphorylation system, but is also a major damage-associated molecular pattern (DAMP) that engages innate immune sensors when released into the cytoplasm, outside of cells or into circulation. As a DAMP, mtDNA not only contributes to anti-viral resistance, but also causes pathogenic inflammation in many disease contexts. Cells experiencing mtDNA stress caused by depletion of the mtDNA-packaging protein, transcription factor A, mitochondrial (TFAM) or during herpes simplex virus-1 infection exhibit elongated mitochondria, enlargement of nucleoids (mtDNA-protein complexes) and activation of cGAS-STING innate immune signalling via mtDNA released into the cytoplasm. However, the relationship among aberrant mitochondria and nucleoid dynamics, mtDNA release and cGAS-STING activation remains unclear. Here we show that, under a variety of mtDNA replication stress conditions and during herpes simplex virus-1 infection, enlarged nucleoids that remain bound to TFAM exit mitochondria. Enlarged nucleoids arise from mtDNA experiencing replication stress, which causes nucleoid clustering via a block in mitochondrial fission at a stage when endoplasmic reticulum actin polymerization would normally commence, defining a fission checkpoint that ensures mtDNA has completed replication and is competent for segregation into daughter mitochondria. Chronic engagement of this checkpoint results in enlarged nucleoids trafficking into early and then late endosomes for disposal. Endosomal rupture during transit through this endosomal pathway ultimately causes mtDNA-mediated cGAS-STING activation. Thus, we propose that replication-incompetent nucleoids are selectively eliminated by an adaptive mitochondria-endosomal quality control pathway that is prone to innate immune system activation, which might represent a therapeutic target to prevent mtDNA-mediated inflammation during viral infection and other pathogenic states.
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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.