ArticleNature communications2021
Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson's disease.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed, 94 citations in OpenAlex.
- The mitochondrial epigenome and noncoding genome in aging and brain diseases.Trends in neurosciences · 2026Review
- The role of cytosolic mitochondrial DNA as a mitochondrial danger signal for stromal fibroblasts in forming the tumor-promoting microenvironment following radiation exposure.Journal of radiation research · 2026Review
- Review
- Neuronal YTHDF2 suppresses innate immune activation in Aβ pathology by promoting mScience advances · 2026Article
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- α-Synuclein aggregates induce mitochondrial damage and trigger innate immunity to drive neuron-microglia communication.Nature communications · 2026Article
- Mitochondrial DNA: a molecular switch driving sterile neuroinflammation.Translational neurodegeneration · 2026Review
- Vagus Nerve Stimulation Attenuates Cognitive Impairment in Traumatic Brain Injury via the mtDNA/cGAS-STING/NLRP3 Inflammasome Axis.Neurocritical care · 2026Article
- Disruption of intracellular iron homeostasis through mitochondrial dysfunction associated with suppression of ATP 13A2 expression.Scientific reports · 2026Article
- The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.Frontiers in cell and developmental biology · 2026Review
- Behavioral and molecular insights into anxiety in ube3a and fmr1 zebrafish models of autism spectrum disorders.Translational psychiatry · 2025Article
- Sensing within: Mitochondrial inside-out signal transduction.Cell chemical biology · 2025Review
- Cytosolic mtDNA and associated EYA-mediated pro-inflammatory signaling modulate healthspan in Drosophila.Research square · 2025Article
- From Ancient Philosophy to Endosymbiotic Theory: The Bacterial Origin and Key Role of Mitochondria in Immune Responses.Microorganisms · 2025Review
- The impact of ERCell death & disease · 2025Article
- Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025Review
- A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies.Molecular neurodegeneration · 2025Article
- Inhibition of ERK1/2 mediated activation of Drp1 alleviates intervertebral disc degeneration via suppressing pyroptosis and apoptosis in nucleus pulposus cells.Journal of orthopaedic translation · 2025Article
- Review
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson's disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.
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.