Mitochondrial complex I activity in microglia sustains neuroinflammation.
Nature
; 628(8006): 195-203, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38480879
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 outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Microglia
/
Electron Transport Complex I
/
Neuroinflammatory Diseases
/
Inflammation
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nature
/
Nature (Lond.)
/
Nature (London)
Year:
2024
Document type:
Article
Country of publication:
Reino Unido