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自噬途径降解肝脏脂滴的研究进展

王蓉芝 王琳雳 焦靖雯 于云飞 李宝龙

引用本文:
Citation:

自噬途径降解肝脏脂滴的研究进展

DOI: 10.12449/JCH240931
基金项目: 

国家自然科学基金面上项目 (81573135);

黑龙江省自然科学基金 (LH2023H056);

黑龙江省博士后科研启动项目 (LBH-Q21042)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:王琳雳、焦靖雯、于云飞负责收集资料;李宝龙、王蓉芝负责课题设计,资料分析,撰写论文,修改论文并最终定稿。
详细信息
    通信作者:

    李宝龙, lbl73@163.com (ORCID: 0009-0008-1930-2224)

Research advances in the degradation of hepatic lipid droplets through the autophagy pathway

Research funding: 

General Project of National Natural Science Foundation of China (81573135);

Natural Science Foundation of Heilongjiang Province of China (LH2023H056);

Heilongjiang Postdoctoral Research Initiation Program (LBH-Q21042)

More Information
    Corresponding author: LI Baolong, lbl73@163.com (ORCID: 0009-0008-1930-2224)
  • 摘要: 自噬是一种高度保守的细胞降解途径,可通过“脂噬”过程来降解脂滴。脂噬可以选择性地识别脂类物质并将其降解,促进β氧化,进而维持细胞内脂质代谢的平衡状态。肝脏通过脂噬信号通路或关键分子来调控脂滴代谢,进而降低肝脏脂肪变性,改善非酒精性脂肪性肝病。本文总结归纳了巨自噬、分子伴侣介导的自噬和微自噬样3种自噬途径降解肝脏脂滴的最新研究进展,AMPK/mTOR-ULK1、ATGL-SIRT1、FGF21-JMJD3、Akt作为调控脂噬过程的主要信号通路,有助于维持肝脂质代谢稳态,能够为临床预防和治疗非酒精性脂肪性肝病提供新思路。

     

  • 图  1  巨自噬信号通路示意图

    Figure  1.  Schematic diagram of the macroautophagy signaling pathway

    图  2  巨自噬和CMA参与脂质代谢示意图

    Figure  2.  Schematic diagram of the involvement of macroautophagy and CMA in lipid metabolism

    表  1  不同自噬形式参与脂滴降解的分子机制

    Table  1.   Molecular mechanisms of different forms of autophagy involved in lipid droplet degradation

    自噬类型 关键分子机制及通路 作用 生物 文献
    巨自噬 ULK1/ATG1 启动自噬体的形成 哺乳动物、酵母 14
    mTOR-ULK1 抑制脂噬 哺乳动物 15
    AMPK-ULK1 促进脂噬 哺乳动物 15
    TFEB 脂噬主要调节因子 哺乳动物 16
    HLH-30、MXL-3 调节脂噬 秀丽隐杆线虫 16
    FgATG15(酵母ATG15同源物) 参与脂滴分解 禾谷镰刀菌 17
    OsATG7(酵母ATG7同源物) 参与脂滴分解 水稻 18
    ATG蛋白 识别脂滴,促进自噬体的形成 酵母、哺乳动物、植物、微藻 19-21
    SNARE蛋白 介导自噬体膜的扩展/闭合 酵母、哺乳动物 22-23
    SQSTM1/p62 桥接脂滴与吞噬泡 哺乳动物 24
    Rab GTP酶 介导脂滴的募集 哺乳动物 25
    CMA HSC70 识别并结合脂滴 哺乳动物 26
    LAMP-2A 结合脂滴并将其移至溶酶体内 哺乳动物 26
    微自噬 ATG6和ATG14 形成脂滴募集位点 酵母 27
    ESCRT蛋白Vps27 将脂滴转移到液泡 酵母 28
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