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 sclerosis 1 . Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells 2 . 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…

• FI
  Fondazione Italiana Sclerosi Multipla

  Award: 2017/B/5
• EC
  European Committee for Treatment and Research in Multiple Sclerosis
• WT
  Wellcome Trust

  Awards: 215888/Z/19/Z, G105713, 215888, 203151/Z/16/Z, 203151
• UR
  UK Research and Innovation

  Awards: MC_PC_17230, MC_UU_00028/4
• AS
  Alzheimer's Society
• CR
  Cancer Research UK
• NI
  National Institute for Health and Care Research
• ET
  Evelyn Trust
• IN
  Isaac Newton Trust

  Awards: RG 97440, 97440
• UD
  UK Dementia Research Institute
• MR
  Medical Research Council

  Awards: MC_PC_17230, MC_UU_00028/4, 220257/Z/20/Z, MC_UU_00028/4, 203151/Z/16/Z
• E
  Erasmus+
• NC
  NIHR Cambridge Biomedical Research Centre