Modulation of the cell membrane lipid milieu by peroxisomal β-oxidation induces Rho1 signaling to trigger inflammatory responses - Aix-Marseille Université Access content directly
Journal Articles Cell Reports Year : 2022

Modulation of the cell membrane lipid milieu by peroxisomal β-oxidation induces Rho1 signaling to trigger inflammatory responses

Brendon D Parsons
Ceileigh M Weaver
Irene Euodia
Juyang Long
Michal Scur
Duncan P Mackenzie
Andrew J Simmonds
Christine A Webber
Richard A Rachubinski
Francesca Di Cara

Abstract

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.
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hal-03763652 , version 1 (29-08-2022)

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Attribution - NonCommercial - NoDerivatives

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Anu S Nath, Brendon D Parsons, Stephanie Makdissi, Rebecca L Chilvers, Yizhu Mu, et al.. Modulation of the cell membrane lipid milieu by peroxisomal β-oxidation induces Rho1 signaling to trigger inflammatory responses. Cell Reports, 2022, 38 (9), pp.110433. ⟨10.1016/j.celrep.2022.110433⟩. ⟨hal-03763652⟩
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