Mitofusin 2 in Macrophages Links Mitochondria! ROS Production, Cytokine Release, Phagocytosis, Autophagy, and Bactericidal Activity
Por:
Tur, J, Pereira-Lopes, S, Vico, T, Marin, EA, Munoz, JP, Hernandez-Alvarez, M, Cardona, PJ, Zorzano, A, Lloberas, J and Celada, A
Publicada:
25 ago 2020
Resumen:
Mitofusin 2 (Mfn2) plays a major role in mitochondrial fusion and in the maintenance of mitochondria-endoplasmic reticulum contact sites. Given that macrophages play a major role in inflammation, we studied the contribution of Mfn2 to the activity of these cells. Pro-inflammatory stimuli such as lipopolysaccharide (LPS) induced Mfn2 expression. The use of the Mfn2 and Mfn1 myeloid-conditional knockout (KO) mouse models reveals that Mfn2 but not Mfn1 is required for the adaptation of mitochondrial respiration to stress conditions and for the production of reactive oxygen species (ROS) upon pro-inflammatory activation. Mfn2 deficiency specifically impairs the production of pro-inflammatory cytokines and nitric oxide. In addition, the lack of Mfn2 but not Mfn1 is associated with dysfunctional autophagy, apoptosis, phagocytosis, and antigen processing. Mfn2(floxed)(;CreLysM) mice fail to be protected from Listeria, Mycobacterium tuberculosis, or LPS endotoxemia. These results reveal an unexpected contribution of Mfn2 to ROS production and inflammation in macrophages.
Filiaciones:
Tur, J:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Macrophage Biol Grp, Barcelona 08028, Spain
Pereira-Lopes, S:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Macrophage Biol Grp, Barcelona 08028, Spain
Vico, T:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Macrophage Biol Grp, Barcelona 08028, Spain
Marin, EA:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Macrophage Biol Grp, Barcelona 08028, Spain
Munoz, JP:
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona 08036, Spain
Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Barcelona 08028, Spain
Hernandez-Alvarez, M:
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona 08036, Spain
Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Barcelona 08028, Spain
:
Inst Germans Trias & Pujol, Unitat TB Expt, Badalona, Spain
Zorzano, A:
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Barcelona 08036, Spain
Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain
Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Barcelona 08028, Spain
Lloberas, J:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Macrophage Biol Grp, Barcelona 08028, Spain
Celada, A:
Univ Barcelona, Fac Biol, Dept Cell Biol Physiol & Immunol, Macrophage Biol Grp, Barcelona 08028, Spain
gold, Green Published
|