Nath 2022 Cell Rep

From Bioblast
Publications in the MiPMap
Nath AS, Parsons BD, Makdissi S, Chilvers RL, Mu Y, Weaver CM, Euodia I, Fitze KA, Long J, Scur M, Mackenzie DP, Makrigiannis AP, Pichaud N, Boudreau LH, Simmonds AJ, Webber CA, Derfalvi B, Hammon Y, Rachubinski RA, Di Cara F (2022) Modulation of the cell membrane lipid milieu by peroxisomal Ξ²-oxidation induces Rho1 signaling to trigger inflammatory responses . Cell Rep 38:110433.

Β» PMID: 35235794 Open Access

Nath Anu S, Parsons Brendon D, Makdissi Stephanie, Chilvers Rebecca L, Mu Yizhu, Weaver Ceileigh M, Euodia Irene, Fitze Katherine A, Long Juyang, Scur Michal, Mackenzie Duncan P, Makrigiannis Andrew P, Pichaud Nicolas, Boudreau Luc H, Simmonds Andrew J, Webber Christine A, Derfalvi Beata, Hammon Yannick, Rachubinski Richard A, Di Cara Francesca (2022) Cell Rep

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. β€’ Keywords: Pex1, Pex2, RhoI/A, Rhogap190, Autoimmune disorders, Cytokine secretion, Cytoskeleton remodeling, Immunometabolism, Peroxisomes, Phospholipids β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CA Moncton Hebert-Chatelain E


Labels: MiParea: Respiration 



Preparation: Permeabilized cells, Intact cells 


Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, Gp, CIV, ROX  HRR: Oxygraph-2k 

2022-03 

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