ArticleNature neuroscience2019
Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration.
Article in Nature neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 342 papers, 3 of them syntheses that pooled it.
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
342 citing papers in PubMed, 3 syntheses or guidelines pooled it, 573 citations in OpenAlex.
- Mitochondrial Transfer in the Neurovascular Unit, Not Only for Energy Rescue: A Systematic Review.Aging and disease · 2024Pooled it
- Meta-analysis of peripheral mean platelet volume in patients with mental disorders: Comparisons in depression, anxiety, bipolar disorder, and schizophrenia.Brain and behavior · 2023Pooled it
- Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta neuropathologica communications · 2023Pooled it
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Disrupted TFEB/GDNF-cAMP/ATP Coupling Underlies Astrocytic Dysfunction and Depression in LRRK2 G2019S Parkinson's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Astrocyte Senescence Disrupts the Extracellular Mitochondrial Compartment and Compromises Bioenergetic Support to Human Neurons.Antioxidants (Basel, Switzerland) · 2026Article
- Accelerated immunostaining of thick biological tissues using bidirectional electric fields with reversible deformation.Biomedical optics express · 2026Article
- ODC1-associated astrocytic urea cycle dysregulation in age-related memory impairment.Biogerontology · 2026Article
- Advances in the clinical application of mesenchymal stem cells for neurological disorders.Stem cell research & therapy · 2026Review
- Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Ferroptosis in depression: mechanisms, association, and therapeutic strategies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Plant-derived mitochondria mitigate aging-related neurodegeneration by reprogramming microglial mitochondrial energy metabolism.Translational neurodegeneration · 2026Article
- Hierarchical Studies in TRAP2 Mice Demonstrate that Neuronal Activation and Mitochondrial Networks Integration Constitute the Key Mechanism Underlying Painful Syncope.Neuroscience bulletin · 2026Article
- Mitochondrial Transport in Bone Metabolism Homeostasis: Molecular Mechanisms and Targeted Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Modulation of mitochondrial dysfunction: Mechanisms and strategies for the use of natural products to treat stroke.Neural regeneration research · 2026Article
- Metabolic reprogramming is critical to microglial activation in Huntington's disease.JCI insight · 2026Article
- Mitochondria transfer in neurological disorders: the key role of neuroglia.Molecular neurodegeneration · 2026Review
- PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damage.bioRxiv : the preprint server for biology · 2026Article
- Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.Molecular neurobiology · 2026Review
- Silicon quantum dots for neurotheranostic applications in dopamine detection.Journal of nanobiotechnology · 2026Review
282 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
In neurodegenerative diseases, debris of dead neurons are thought to trigger glia-mediated neuroinflammation, thus increasing neuronal death. Here we show that the expression of neurotoxic proteins associated with these diseases in microglia alone is sufficient to directly trigger death of naive neurons and to propagate neuronal death through activation of naive astrocytes to the A1 state. Injury propagation is mediated, in great part, by the release of fragmented and dysfunctional microglial mitochondria into the neuronal milieu. The amount of damaged mitochondria released from microglia relative to functional mitochondria and the consequent neuronal injury are determined by Fis1-mediated mitochondrial fragmentation within the glial cells. The propagation of the inflammatory response and neuronal cell death by extracellular dysfunctional mitochondria suggests a potential new intervention for neurodegeneration-one that inhibits mitochondrial fragmentation in microglia, thus inhibiting the release of dysfunctional mitochondria into the extracellular milieu of the brain, without affecting the release of healthy neuroprotective mitochondria.
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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.