线粒体动力学和线粒体自噬的分子机制及其在神经退行性疾病中的作用

刘慧, 张自弘, 鲍秀琦, 张丹

中国药学杂志 ›› 2020, Vol. 55 ›› Issue (5) : 337-341.

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中国药学杂志
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中国药学杂志 ›› 2020, Vol. 55 ›› Issue (5) : 337-341. DOI: 10.11669/cpj.2020.05.002
综述

线粒体动力学和线粒体自噬的分子机制及其在神经退行性疾病中的作用

  • 刘慧, 张自弘, 鲍秀琦*, 张丹*
作者信息 +

Molecular Mechanisms of Mitochondrial Dynamics and Mitophagy and Their Roles in Neurodegenerative Diseases

  • LIU Hui, ZHANG Zi-hong, BAO Xiu-qi*, ZHANG Dan*
Author information +
文章历史 +

摘要

线粒体是维持细胞代谢过程的关键细胞器,因此线粒体质量控制对于细胞命运具有决定性作用。线粒体动力学和线粒体自噬是线粒体质量控制的主要机制。在神经系统中,线粒体动力学对于维持线粒体的正常形态及神经元的功能至关重要。而线粒体自噬能够及时清除损伤线粒体,维持神经元内线粒体稳态。线粒体动力学异常及自噬障碍最终会导致神经元损伤。近年来,越来越多的证据表明,线粒体动力学失衡及自噬障碍在神经退行性疾病中普遍存在。笔者主要讨论了线粒体动力学和线粒体自噬的分子机制,阐明了其在神经退行性疾病发病中的作用,调控线粒体动力学和线粒体自噬可能成为治疗神经退行性疾病的关键靶点。

Abstract

Mitochondria are high dynamic organelles in living cells that maintain cellular metabolic processes and therefore mitochondrial quality control, which play an important role in the maintenance of intracellular homeostasis, is crucial for cell survival. It was reported that mitochondrial dynamics and mitophagy are two main mechanisms in the regulation of mitochondrial quality control. In the central nervous system, maintenance of mitochondrial function and morphology requires fission and fusion of these dynamic organelles. Mitophagy, a selective form of autophagy, which removes abnormal and dysfunctional mitochondria, plays an indispensable role in regulating mitochondrial homeostasis in neurons. Once these systems are disrupted, dysfunctional mitochondria accumulate and potentiate neuronal death, which is associated with reduced levels of ATP and excessive production of reactive oxygen species (ROS). In recent years, there has been increasing evidence suggesting that mitochondrial dynamics imbalance and mitophagy disorders are involved in the pathophysiology of neurodegenerative diseases. In this review, the most recent progress on the molecular mechanisms of mitochondrial dynamics and mitophagy was discussed their roles on the pathological process of neurodegenerative diseases was focused. Elucidation of the regulation of mitochondrial dynamics and mitophagy may become new targets for the treatment of neurodegenerative diseases.

关键词

线粒体动力学 / 线粒体自噬 / 分子机制 / 神经退行性疾病

Key words

mitochondrial dynamics / mitophagy / molecular mechanisms / neurodegenerative diseases

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刘慧, 张自弘, 鲍秀琦, 张丹. 线粒体动力学和线粒体自噬的分子机制及其在神经退行性疾病中的作用[J]. 中国药学杂志, 2020, 55(5): 337-341 https://doi.org/10.11669/cpj.2020.05.002
LIU Hui, ZHANG Zi-hong, BAO Xiu-qi, ZHANG Dan. Molecular Mechanisms of Mitochondrial Dynamics and Mitophagy and Their Roles in Neurodegenerative Diseases[J]. Chinese Pharmaceutical Journal, 2020, 55(5): 337-341 https://doi.org/10.11669/cpj.2020.05.002
中图分类号： R963   

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基金

国家自然科学基金项目资助(81630097, 81773718);重大新药创制科技重大专项十三五计划资助(2018ZX09711001-003-020,2018ZX09711001-003-005,2018ZX09711001-008-005);医科院创新工程重大协同创新项目资助(500104122);中国医学科学院中央高校基本科研业务费资助(2018RC35002);中国医学科学院医学与健康科技创新工程项目资助(2016-I2M-3-011)
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