Mitochondrial complex I activity in microglia sustains neuroinflammation.

ABSTRACT: Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis¹. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells². However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional ou

SUBMITTER: Peruzzotti-Jametti L 

PROVIDER: S-EPMC10990929 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature