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

Function (Oxf). 2024 Jul 11;5(4):zqae019. doi: 10.1093/function/zqae019.

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.

Keywords: P2X7 receptor; inflammation; microglia; microparticles; mitochondria.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Line
  • Cell-Derived Microparticles* / metabolism
  • Mice
  • Mice, Knockout*
  • Microglia* / metabolism
  • Mitochondria* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Receptors, Purinergic P2X7* / genetics
  • Receptors, Purinergic P2X7* / metabolism

Substances

  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • P2rx7 protein, mouse
  • Nlrp3 protein, mouse