Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy.
Center of Electronic Microscopy, University of Ferrara, Ferrara 44121, Italy.
Function (Oxf). 2021 Jan 28;2(2):zqab005. doi: 10.1093/function/zqab005. eCollection 2021.
Basal expression of the P2X7 receptor (P2X7R) improves mitochondrial metabolism, Adenosine 5'-triphosphate (ATP) synthesis, and overall fitness of immune and non-immune cells. We investigated P2X7R contribution to energy metabolism and subcellular localization in fibroblasts (mouse embryo fibroblasts and HEK293 human fibroblasts), mouse microglia (primary brain microglia, and the N13 microglia cell line), and heart tissue. The P2X7R localizes to mitochondria, and its lack (1) decreases basal respiratory rate, ATP-coupled respiration, maximal uncoupled respiration, resting mitochondrial potential, mitochondrial matrix Ca level, (2) modifies expression pattern of oxidative phosphorylation enzymes, and (3) severely affects cardiac performance. Hearts from -deleted versus wild-type mice are larger, heart mitochondria smaller, and stroke volume, ejection fraction, fractional shortening, and cardiac output, are significantly decreased. Accordingly, the physical fitness of P2X7R-null mice is severely reduced. Thus, the P2X7R is a key modulator of mitochondrial energy metabolism and a determinant of physical fitness.
P2X7 受体（P2X7R）的基础表达可改善免疫和非免疫细胞的线粒体代谢、三磷酸腺苷（ATP）合成和整体适应性。我们研究了 P2X7R 对成纤维细胞（小鼠胚胎成纤维细胞和 HEK293 人成纤维细胞）、小鼠小胶质细胞（原代脑小胶质细胞和 N13 小胶质细胞系）和心脏组织中的能量代谢和亚细胞定位的贡献。P2X7R 定位于线粒体，其缺乏（1）降低基础呼吸率、ATP 偶联呼吸、最大解偶联呼吸、静息线粒体电位、线粒体基质 Ca 水平，（2）改变氧化磷酸化酶的表达模式，（3）严重影响心脏功能。与野生型相比，-/- 基因敲除型小鼠的心脏更大，心脏线粒体更小，而每搏输出量、射血分数、缩短分数和心输出量明显降低。因此，P2X7R 基因敲除型小鼠的身体适应性严重降低。因此，P2X7R 是线粒体能量代谢的关键调节剂，也是身体适应性的决定因素。
