P2X7-dependent exchange of extracellular microparticles and mitochondria by mouse microglia

Abstract

Microparticles (MPs) are ubiquitously secreted by all cells and play a fundamental role in numerous biological processes such as cell-to-cell communication, cell differentiation, inflammation, and cell energy transfer. Ligation of the P2X7 receptor (P2X7R) by extracellular ATP (eATP) is the well-known stimulus for MP release, which affects their contents in a cell-specific fashion. We investigated MP release and functional impact in mouse microglial cell lines characterized for high (N13-P2X7RHigh) or low (N13-P2X7RLow) expression of the P2X7R. Stimulation with extracellular ATP triggered a P2X7R-dependent release of a 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. Other constituents of the MP cargo, e.g. NLRP3 and the P2X7R itself, were also delivered to the recipient cells. Transfer of mitochondria, NLRP3 and P2X7R increased the energy level of the recipient cells and conferred a pro-inflammatory phenotype. These data show that P2X7R-dependent exchange of MPs and mitochondria modulates energy metabolism and inflammatory responses, pointing to the P2X7R as a master regulator of intercellular organelle and MP trafficking in mouse microglia.