Activation of the purinergic receptor P2X7 improves hepatosteatosis by promoting lipophagy

FEBS Letters

article

Zizhi Dong¹  Yujia Wei²  Min Tao¹  Lili Zhang¹ 

[1] Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University;Department of Radiology, Mayo Clinic

关键词: autophagy;    lipophagy;    nonalcoholic fatty liver disease;    purinergic receptor P2X7;   

DOI  :  10.1002/1873-3468.14207

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown