Mitochondrial complex I inhibition enhances astrocyte responsiveness to pro-inflammatory stimuli.

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 inhibiti

SUBMITTER: Wischhof L 

PROVIDER: S-EPMC11549212 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature