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The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia
Simonetta Falzoni1, Valentina Vultaggio-Poma1, Paola Chiozzi1
1Department of Medical Sciences, University of Ferrara, 44100 Ferrara, Italy.
Abstract:
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.
Insights
Extracellular ATP (ATP) triggers microglial cells to release microparticles (MPs) containing mitochondria, NLRP3, and the P2X7 receptor (P2X7R). This transfer enhances recipient cell energy and promotes inflammation.
Area of Science:
- Immunology
- Cell Biology
- Neuroscience
Background:
- Microparticles (MPs) mediate intercellular communication, differentiation, inflammation, and energy transfer.
- P2X7 receptor (P2X7R) activation by extracellular ATP (eATP) significantly influences MP release and content.
Purpose of the Study:
- To investigate P2X7R-mediated microparticle release and functional impact in microglial cells.
- To characterize the role of P2X7R in intercellular organelle trafficking.
Main Methods:
- Utilized P2X7R-WT and P2X7R-KO mice microglial cells.
- Employed mouse microglial cell lines with high (N13-P2X7RHigh) and low (N13-P2X7RLow) P2X7R expression.
- Analyzed microparticle release, content, and recipient cell functional changes.
Main Results:
- P2X7R stimulation induced microparticle release enriched with naked mitochondria.
- Mitochondria, NLRP3, and P2X7R were transferred to recipient cells in a P2X7R-dependent manner.
- Microparticle transfer boosted recipient cell energy levels and induced a pro-inflammatory phenotype.
Conclusions:
- P2X7R activation is a key regulator of intercellular organelle and microparticle trafficking in immune cells.
- Mitochondrial transfer via MPs contributes to recipient cell bioenergetics and inflammatory responses.
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