ArticleScientific reports2024
Mitochondrial complex I inhibition enhances astrocyte responsiveness to pro-inflammatory stimuli.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Astrocyte Senescence Disrupts the Extracellular Mitochondrial Compartment and Compromises Bioenergetic Support to Human Neurons.Antioxidants (Basel, Switzerland) · 2026Article
- ALS-FTD-linked CCNFJournal of neuroinflammation · 2026Article
- The hypothalamus is an early site of mitochondrial failure and neuro-immune circuit disruption in amyotrophic lateral sclerosis.Molecular metabolism · 2026Article
- Astrocyte epigenetics as a priority area in neuroscience research.Frontiers in molecular neuroscience · 2025Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of the mitochondrial oxidative phosphorylation (OXPHOS) system can lead to metabolic disorders and neurodegenerative diseases. In primary mitochondrial disorders, reactive astrocytes often accompany neuronal degeneration and may contribute to neurotoxic inflammatory cascades that elicit brain lesions. The influence of mitochondria to astrocyte reactivity as well as the underlying molecular mechanisms remain elusive. Here we report that mitochondrial Complex I dysfunction promotes neural progenitor cell differentiation into astrocytes that are more responsive to neuroinflammatory stimuli. We show that the SWItch/Sucrose Non-Fermentable (SWI/SNF/BAF) chromatin remodeling complex takes part in the epigenetic regulation of astrocyte responsiveness, since its pharmacological inhibition abrogates the expression of inflammatory genes. Furthermore, we demonstrate that Complex I deficient human iPSC-derived astrocytes negatively influence neuronal physiology upon cytokine stimulation. Together, our data describe the SWI/SNF/BAF complex as a sensor of altered mitochondrial OXPHOS and a downstream epigenetic regulator of astrocyte-mediated neuroinflammation.
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