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The mitochondrial succinate dehydrogenase complex controls the STAT3-IL-10 pathway in inflammatory macrophages.
Gobelli, Dino; Serrano-Lorenzo, Pablo; Esteban-Amo, María J; Serna, Julia; Pérez-García, M Teresa; Orduña, Antonio; Jourdain, Alexis A; Martín-Casanueva, Miguel Á; Á de la Fuente, Miguel; Simarro, María.
Afiliación
  • Gobelli D; Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain.
  • Serrano-Lorenzo P; Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid and Spanish National Research Council (CSIC), 47003 Valladolid, Spain.
  • Esteban-Amo MJ; Hospital 12 de Octubre Research Institute (imas12), 28041 Madrid, Spain.
  • Serna J; Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
  • Pérez-García MT; Mitochondrial Disorders Laboratory, Clinical Biochemistry Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
  • Orduña A; Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain.
  • Jourdain AA; Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid and Spanish National Research Council (CSIC), 47003 Valladolid, Spain.
  • Martín-Casanueva MÁ; Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid and Spanish National Research Council (CSIC), 47003 Valladolid, Spain.
  • Á de la Fuente M; Department of Biochemistry and Molecular Biology and Physiology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain.
  • Simarro M; Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid and Spanish National Research Council (CSIC), 47003 Valladolid, Spain.
iScience ; 26(8): 107473, 2023 Aug 18.
Article en En | MEDLINE | ID: mdl-37575201
ABSTRACT
The functions of macrophages are tightly regulated by their metabolic state. However, the role of the mitochondrial electron transport chain (ETC) in macrophage functions remains understudied. Here, we provide evidence that the succinate dehydrogenase (SDH)/complex II (CII) is required for respiration and plays a role in controlling effector responses in macrophages. We find that the absence of the catalytic subunits Sdha and Sdhb in macrophages impairs their ability to effectively stabilize HIF-1α and produce the pro-inflammatory cytokine IL-1ß in response to LPS stimulation. We also arrive at the novel result that both subunits are essential for the LPS-driven production of IL-10, a potent negative feedback regulator of the macrophage inflammatory response. This phenomenon is explained by the fact that the absence of Sdha and Sdhb leads to the inhibition of Stat3 tyrosine phosphorylation, caused partially by the excessive accumulation of mitochondrial reactive oxygen species (mitoROS) in the knockout cells.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: España

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: IScience Año: 2023 Tipo del documento: Article País de afiliación: España