线粒体损伤在非酒精性脂肪性肝病发生发展中的作用

肖卫纯; 安威

doi:10.3969/j.issn.1001-5256.2021.07.005

线粒体损伤在非酒精性脂肪性肝病发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.07.005

肖卫纯,
安威^,

首都医科大学细胞生物学系肝脏保护与再生调节北京市重点实验室，北京 100069

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：肖卫纯起草文章内容；安威提供思路与框架，修改并校对文章。

详细信息

通信作者:
安威，anwei@ccmu.edu.cn

中图分类号: R575.5
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出版历程
- 收稿日期: 2021-04-24
- 录用日期: 2021-04-24
- 出版日期: 2021-07-20

Role of mitochondrial injury in the development and progression of nonalcoholic fatty liver disease

Weichun XIAO,
Wei AN^,

Beijing Key Laboratory of Liver Protection and Regulation of Regeneration, Department of Cell Biology, Capital Medical University, Beijing 100069, China

摘要

摘要: 线粒体是重要的细胞器，调节细胞脂质代谢、氧化磷酸化和ATP合成。线粒体生物合成障碍、稳态失衡乃至结构破坏都将导致脂质代谢紊乱以及氧化应激。非酒精性脂肪性肝病(NAFLD)是肝细胞脂质堆积为特征的慢性肝病。NAFLD是一个进展性疾病，表现为肝细胞脂肪变、脂肪性肝炎、肝纤维化和肝硬化这一轴向过程。目前认为线粒体在NAFLD发病中发挥着重要作用，NAFLD也被称为“线粒体病”。综述了脂质代谢障碍、氧化应激、线粒体稳态失衡等线粒体损伤与NAFLD发生发展的相关性。
- 线粒体 /
- 非酒精性脂肪性肝病 /
- 脂类代谢
Abstract: Mitochondria are an important organelle and can regulate lipid metabolism, oxidative phosphorylation, and ATP synthesis. Disorder of mitochondria biosynthesis, loss of mitochondrial homeostasis, and even mitochondrial structural damage will lead to lipid metabolism disorders and oxidative stress. Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by lipid accumulation in hepatocytes. NAFLD is a progressive disease manifesting as the process from hepatocyte steatosis to steatohepatitis, liver fibrosis, and liver cirrhosis. It is currently believed that mitochondria play an important role in the onset of NAFLD, and thus NAFLD is also referred to as "mitochondrial disease". This article reviews the association of mitochondrial injury, such as lipid metabolism disorders, change in reactive oxygen species, and loss of mitochondrial homeostasis, with the development and progression of NAFLD.
- Mitochondria /
- Non-alcoholic Fatty Liver Disease /
- Lipid Metabolism

HTML全文

图 1 线粒体与脂类代谢

注：Ⅰ、Ⅱ、Ⅲ和Ⅳ：电子传递链复合物Ⅰ、Ⅱ、Ⅲ和Ⅳ；CytC：细胞色素C。长链脂肪酸通过脂酰CoA合成酶催化为脂酰CoA，由CPT-1催化与肉碱结合为脂酰肉碱进入膜间隙，生成的脂酰肉碱在肉碱-脂酰肉碱转位酶的作用下进入基质，由CPT-2催化重新分解为脂酰CoA和肉碱；脂酰CoA经β-氧化生成乙酰CoA，乙酰CoA经过三羧酸循环彻底氧化。由β-氧化和三羧酸循环产生的氢离子以NADH和FADH2为递氢体，通过ETC传递链传递电子，耦联质子从线粒体基质泵入膜间隙，产生跨内膜的电化学梯度，当质子通过ATP酶复合体中的质子通道进入基质时，ATP合酶利用电化学质子梯度的能量催化ADP与Pi合成ATP，产生H₂O。

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图 2 线粒体脂类代谢障碍与脂肪堆积

注：肝脏所吸收的脂肪主要在肝脏进行代谢。CPT-1是脂肪酸转运的限速酶，催化长链脂肪酸由胞质转入线粒体进行β-氧化。CPT-1表达或活性下降导致脂肪堆积；脂肪酸在线粒体通过β-氧化分解为乙酰CoA, 转运出线粒体，在胞浆中参与脂质从头合成，合成的丙二酰CoA抑制CPT-1的活性，并且受到AMPK的调节; AMPK活性增加，导致ACC磷酸化而活性下降，丙二酰CoA合成减少，CPT-1的活性增加；AMPK活性降低时，SREBP活性增强，脂类合成(ACC, FAS)和胆固醇合成的相关蛋白和酶类增加，促进脂质和胆固醇合成，导致脂质堆积。PGC-1通过NRF1/2、ERR等转录因子调节线粒体电子传递链的生物合成以及FAO和氧化磷酸化所需酶类；活性增高时，促进CPT-1的表达，FAO增多。

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