ArticleNature communications2018
Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Brain mitochondria as key drivers of cognition and behaviour.Nature reviews. Neuroscience · 2026Review
- The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.Molecular and cellular biochemistry · 2026Review
- Loss of mitochondrial DNA helicase in retinal macroglia drives neovascular retinopathy.EMBO molecular medicine · 2026Article
- miR-27a Suppresses Mitochondrial Function to Promote Hepatic Steatosis in High-Fat-Diet-Induced Obesity.Molecules (Basel, Switzerland) · 2026Article
- Mitochondrial DNA Damage in Substantia Nigra Pars Compacta Astrocytes Exacerbates Dopaminergic Neuron Loss in a 6-Hydroxydopamine Mouse Model of Parkinsonism.Cellular and molecular neurobiology · 2026Article
- N-Acetylglucosamine Selectively Attenuates Neuroinflammation in a Mouse Model of Mitochondrial Dysfunction.Acta physiologica (Oxford, England) · 2026Article
- Nicotinamide riboside reduces glial inflammation and boosts mitochondrial function.International journal of biological sciences · 2026Article
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Mitochondrial fission controls astrocyte morphogenesis and organization in the cortex.The Journal of cell biology · 2025Article
- Stabilizing a mammalian RNA thermometer confers neuroprotection in subarachnoid hemorrhage.Nature communications · 2025Article
- Gene therapy prevents hepatic mitochondrial dysfunction in murine deoxyguanosine kinase deficiency.Molecular therapy. Methods & clinical development · 2025Article
- Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia.Molecular medicine (Cambridge, Mass.) · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Heterogeneous brain region-specific responses to astrocytic mitochondrial DNA damage in mice.Scientific reports · 2024Article
- Hallmark Molecular and Pathological Features of POLG Disease are Recapitulated in Cerebral Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Most axonal mitochondria in cortical pyramidal neurons lack mitochondrial DNA and consume ATP.bioRxiv : the preprint server for biology · 2024Article
- Activation of Neurotoxic Astrocytes Due to Mitochondrial Dysfunction Triggered byInternational journal of biological sciences · 2024Article
- Metabolic dynamics in astrocytes and microglia during post-natal development and their implications for autism spectrum disorders.Frontiers in cellular neuroscience · 2024Review
- The NADInternational journal of biological sciences · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying the clinical variability remain poorly understood. To clarify whether different brain cells have differential sensitivity to mitochondrial dysfunction, we induced mitochondrial DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), the replicative mtDNA helicase. Here we show that astrocytes, the most abundant cerebral cell type, are chronically activated upon mtDNA loss, leading to early-onset spongiotic degeneration of brain parenchyma, microgliosis and secondary neurodegeneration. Neuronal mtDNA loss does not, however, cause symptoms until 8 months of age. Findings in astrocyte-TwKO mimic neuropathology of Alpers syndrome, infantile-onset mitochondrial spongiotic encephalopathy caused by mtDNA maintenance defects. Our evidence indicates that (1) astrocytes are dependent on mtDNA integrity; (2) mitochondrial metabolism contributes to their activation; (3) chronic astrocyte activation has devastating consequences, underlying spongiotic encephalopathy; and that (4) astrocytes are a potential target for interventions.
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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.