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  2. BNIP3 in hypoxia-induced mitophagy: novel insights and promising target for non-alcoholic fatty liver disease

BNIP3 in hypoxia-induced mitophagy: novel insights and promising target for non-alcoholic fatty liver disease

  • Int J Biochem Cell Biol. 2024 Jan 10:106517. doi: 10.1016/j.biocel.2024.106517.
Meiyuan Tian 1 Jing Hou 2 Zhe Liu 1 Zhanquan Li 2 Dengliang Huang 2 Yaogang Zhang 2 Yanyan Ma 3
Affiliations

Affiliations

  • 1 Research Center for High Altitude Medicine, Key Laboratory of High-Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining 810001, China; Central Laboratory, Affiliated Hospital of Qinghai University in Qinghai province, Xining, 810001, China; Key Laboratory for Echinococcosis studies in Qinghai Province, Xining, 810001, China.
  • 2 Central Laboratory, Affiliated Hospital of Qinghai University in Qinghai province, Xining, 810001, China; Key Laboratory for Echinococcosis studies in Qinghai Province, Xining, 810001, China.
  • 3 Research Center for High Altitude Medicine, Key Laboratory of High-Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining 810001, China; Central Laboratory, Affiliated Hospital of Qinghai University in Qinghai province, Xining, 810001, China; Key Laboratory for Echinococcosis studies in Qinghai Province, Xining, 810001, China. Electronic address: mayanyan_research@qhu.edu.cn.
Abstract

BNIP3 localizes to the outer mitochondrial membrane, has been demonstrated to be extensively involved in abnormalities to mitochondrial metabolic function and dynamicsand in non-alcoholic fatty liver disease (NAFLD). However, its role in NAFLD under hypoxia remains unclear. This study aimed to investigate the expression and the role of BNIP3 in NAFLD under hypoxia, and explore its involvement in regulating NAFLD Mitophagy, fatty acid β-oxidation both in vivo and in vitro. BNIP3-mediated Mitophagy level was analyzed using real-time quantitative polymerase chain reaction, Western blotting, immunofluorescence and electron microscopy. The role of BNIP3 in fatty acid β-oxidation was evaluated using lipid droplet staining, triglyceride content determination, and cellular energy metabolism. The results showed that compared with the HFD-2200 m, the body weight, inflammatory liver injury, and lipid deposition were significantly reduced in the HFD-4500 m group (P<0.05), but Autophagy and Mitophagy were increased, and the expression of the Mitophagy receptor BNIP3 was increased (P<0.05). Compared to the control group, BNIP3 knockdown in the hypoxia group resulted in decreased levels of CPT1, ATGL, and p-HSL in lipid-accumulating hepatocytes, lipid droplet accumulation and triglyceride content increased (P<0.05). Moreover, the ability of lipid-accumulating hepatocytes to oxidize fatty acids was reduced by BNIP3 knockdown in the hypoxia group (P<0.05). Therefore, it can be concluded that, in NAFLD mice under hypoxia, BNIP3-mediated Mitophagy promotes fatty acid β-oxidation. This study elucidated the role of BNIP3 in promoting fatty acid β-oxidation in NAFLD under hypoxia, and suggests BNIP3 may serve as a novel potential therapeutic target for NAFLD.

Keywords

BNIP3; NAFLD; hypoxia; mitophagy; β-oxidation.

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