Activation of the purinergic receptor P2X7 improves hepatosteatosis by promoting lipophagy,FEBS Letters

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Activation of the purinergic receptor P2X7 improves hepatosteatosis by promoting lipophagy
FEBS Letters ( IF 3.0 ) Pub Date : 2021-10-15 , DOI: 10.1002/1873-3468.14207
Zizhi Dong ₁ , Yujia Wei ₂ , Min Tao ₁ , Lili Zhang ₁

Affiliation

Nonalcoholic fatty liver disease (NAFLD) is a global health problem that develops through unclear molecular mechanisms. The P2X7 purinergic receptor (P2RX7) is an ATP-gated ion channel that belongs to the P2XR family. Thus far, studies on P2RX7 in NAFLD have been largely contradictory. Integrating experiments and modeling, we elucidate the dynamic processes of lipid droplet fusion and degradation following regulation of P2RX7. We show that activation of P2RX7 can activate the AMPK/ULK1 pathway to promote autophagosome generation and lysosomal degradation of autophagosomes. Inhibiting P2RX7 has the opposite effect. Notably, we find that lipid droplets become larger by the fusion of dysfunctional lysosomes but cannot be degraded by them following P2RX7 inhibition. Our study provides evidence that P2RX7 activation improves NAFLD by promoting lipophagy.

中文翻译：

嘌呤能受体 P2X7 的激活通过促进脂肪吞噬来改善肝脂肪变性

非酒精性脂肪性肝病 (NAFLD) 是一种全球性的健康问题，其分子机制不明。P2X7 嘌呤能受体 (P2RX7) 是一种 ATP 门控离子通道，属于 P2XR 家族。迄今为止，对 NAFLD 中 P2RX7 的研究在很大程度上是相互矛盾的。结合实验和建模，我们阐明了 P2RX7 调控后脂滴融合和降解的动态过程。我们表明 P2RX7 的激活可以激活 AMPK/ULK1 通路以促进自噬体的产生和自噬体的溶酶体降解。抑制 P2RX7 具有相反的效果。值得注意的是，我们发现脂滴通过功能失调的溶酶体的融合变大，但在 P2RX7 抑制后不能被它们降解。

更新日期：2021-11-22

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