Microglia mitochondrial complex I deficiency during development induces glial dysfunction and early lethality
Nicolás Capelo Carrasco, Bella Mora-Romero, Juan J. Perez-Moreno, Maria I. Alvarez-Vergara, Laura Trujillo-Estrada, Carmen Romero-Molina, Emilio Martinez-Marquez, Noelia Morano-Catalan, Marisa Vizuete, Jose Lopez-Barneo, Jose L. Nieto-Gonzalez, Pablo Garcia-Junco-Clemente, Javier Vitorica, Antonia Gutierrez, David Macias, Alicia E. Rosales-Nieves, Alberto Pascual · FENS Forum 2024
Primary mitochondrial diseases (PMDs) associate with pediatric neurological disorders and are traditionally related to oxidative phosphorylation system (OXPHOS) defects in neurons. Interestingly, both PMD mouse models and patients also show gliosis, and pharmacologic depletion of microglia, the brain resident innate immunity, ameliorate the multiple symptoms of a mouse model. Since microglia activation correlates with the expression of OXPHOS genes, we studied whether OXPHOS deficits in microglia may contribute to PMDs. We first observed that the metabolic rewiring associated to microglia IL-3