Modulation of the cell membrane lipid milieu by peroxisomal β-oxidation induces Rho1 signaling to trigger inflammatory responses
| Autor: | Anu S. Nath, Brendon D. Parsons, Stephanie Makdissi, Rebecca L. Chilvers, Yizhu Mu, Ceileigh M. Weaver, Irene Euodia, Katherine A. Fitze, Juyang Long, Michal Scur, Duncan P. Mackenzie, Andrew P. Makrigiannis, Nicolas Pichaud, Luc H. Boudreau, Andrew J. Simmonds, Christine A. Webber, Beata Derfalvi, Yannick Hamon, Richard A. Rachubinski, Francesca Di Cara |
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| Přispěvatelé: | DUMENIL, Anita, Dalhousie University [Halifax], Department of Chemistry and Biochemistry, Université de Moncton, University of Alberta, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Pex1
cytokine secretion [SDV]Life Sciences [q-bio] immunometabolism peroxisomes Glycerophospholipids cytoskeleton remodeling Lipid Metabolism General Biochemistry Genetics and Molecular Biology autoimmune disorders Pex2 [SDV] Life Sciences [q-bio] Membrane Lipids Mice Animals Humans Rhogap190 RhoI/A phospholipids Signal Transduction |
| Zdroj: | Cell Reports Cell Reports, 2022, 38 (9), pp.110433. ⟨10.1016/j.celrep.2022.110433⟩ |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2022.110433⟩ |
| Popis: | International audience; Phagocytosis, signal transduction, and inflammatory responses require changes in lipid metabolism. Peroxisomes have key roles in fatty acid homeostasis and in regulating immune function. We find that Drosophila macrophages lacking peroxisomes have perturbed lipid profiles, which reduce host survival after infection. Using lipidomic, transcriptomic, and genetic screens, we determine that peroxisomes contribute to the cell membrane glycerophospholipid composition necessary to induce Rho1-dependent signals, which drive cytoskeletal remodeling during macrophage activation. Loss of peroxisome function increases membrane phosphatidic acid (PA) and recruits RhoGAPp190 during infection, inhibiting Rho1-mediated responses. Peroxisome-glycerophospholipid-Rho1 signaling also controls cytoskeleton remodeling in mouse immune cells. While high levels of PA in cells without peroxisomes inhibit inflammatory phenotypes, large numbers of peroxisomes and low amounts of cell membrane PA are features of immune cells from patients with inflammatory Kawasaki disease and juvenile idiopathic arthritis. Our findings reveal potential metabolic markers and therapeutic targets for immune diseases and metabolic disorders. |
| Databáze: | OpenAIRE |
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