The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia

• Published in: Function (Oxford, England) Vol. 5; no. 4
• Main Authors: Falzoni, Simonetta, Vultaggio-Poma, Valentina, Chiozzi, Paola, Tarantini, Mario, Adinolfi, Elena, Boldrini, Paola, Giuliani, Anna Lisa, Morciano, Giampaolo, Tang, Yong, Gorecki, Dariusz C, Di Virgilio, Francesco
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 11.07.2024
• Subjects: Adenosine Triphosphate - metabolism; Animals; Cell differentiation; Cell interactions; Cell Line; Cell lines; Cell-Derived Microparticles - metabolism; Mice; Mice, Knockout; Microglia; Microglia - metabolism; Microparticles; Mitochondria; Mitochondria - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Original Research; Phenotypes; Receptors, Purinergic P2X7 - genetics; Receptors, Purinergic P2X7 - metabolism; microparticles; inflammation; P2X7 receptor; microglia; mitochondria
• ISSN: 2633-8823; 2633-8823
• DOI: 10.1093/function/zqae019

Microparticles (MPs) are secreted by all cells, where they play a key role in intercellular communication, differentiation, inflammation, and cell energy transfer. P2X7 receptor (P2X7R) activation by extracellular ATP (eATP) causes a large MP release and affects their contents in a cell-specific fashion. We investigated MP release and functional impact in microglial cells from P2X7R-WT or P2X7R-KO mice, as well as mouse microglial cell lines characterized for high (N13-P2X7RHigh) or low (N13-P2X7RLow) P2X7R expression. P2X7R stimulation promoted release of a mixed MP population enriched with naked mitochondria. Released mitochondria were taken up and incorporated into the mitochondrial network of the recipient cells in a P2X7R-dependent fashion. NLRP3 and the P2X7R itself were also delivered to the recipient cells. Microparticle transfer increased the energy level of the recipient cells and conferred a pro-inflammatory phenotype. These data show that the P2X7R is a master regulator of intercellular organelle and MP trafficking in immune cells. Graphical Abstract Graphical Abstract