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Mitochondrial complex I activity in microglia sustains neuroinflammation.
Peruzzotti-Jametti, L; Willis, C M; Krzak, G; Hamel, R; Pirvan, L; Ionescu, R-B; Reisz, J A; Prag, H A; Garcia-Segura, M E; Wu, V; Xiang, Y; Barlas, B; Casey, A M; van den Bosch, A M R; Nicaise, A M; Roth, L; Bates, G R; Huang, H; Prasad, P; Vincent, A E; Frezza, C; Viscomi, C; Balmus, G; Takats, Z; Marioni, J C; D'Alessandro, A; Murphy, M P; Mohorianu, I; Pluchino, S.
Afiliação
  • Peruzzotti-Jametti L; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. lp429@cam.ac.uk.
  • Willis CM; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. lp429@cam.ac.uk.
  • Krzak G; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Hamel R; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Pirvan L; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Ionescu RB; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Reisz JA; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Prag HA; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USA.
  • Garcia-Segura ME; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Wu V; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Xiang Y; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Barlas B; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Casey AM; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • van den Bosch AMR; UK Dementia Research Institute, University of Cambridge, Cambridge, UK.
  • Nicaise AM; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Roth L; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Bates GR; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Huang H; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Prasad P; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Vincent AE; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Frezza C; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Viscomi C; Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Balmus G; University Hospital Cologne, Cologne, Germany.
  • Takats Z; University of Padua, Padova, Italy.
  • Marioni JC; Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • D'Alessandro A; UK Dementia Research Institute, University of Cambridge, Cambridge, UK.
  • Murphy MP; Department of Molecular Neuroscience, Transylvanian Institute of Neuroscience, Cluj-Napoca, Romania.
  • Mohorianu I; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Pluchino S; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Genome Campus, Hinxton, UK.
Nature ; 628(8006): 195-203, 2024 Apr.
Article em 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Complexo I de Transporte de Elétrons / Doenças Neuroinflamatórias / Inflamação Limite: Animals / Female / Humans / Male Idioma: En Revista: Nature Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microglia / Complexo I de Transporte de Elétrons / Doenças Neuroinflamatórias / Inflamação Limite: Animals / Female / Humans / Male Idioma: En Revista: Nature Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Reino Unido