Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, China.
Mol Biol Rep. 2022 Nov;49(11):10749-10760. doi: 10.1007/s11033-022-07738-x. Epub 2022 Jul 6.
Mitochondria dysfunction has been defined as one of the hallmarks of aging-related diseases as is characterized by the destroyed integrity, abnormal distribution and size, insufficient ATP supply, increased ROS production, and subsequently damage and oxidize the proteins, lipids and nucleic acid. Mitophagy, an efficient way of removing damaged or defective mitochondria by autophagy, plays a pivotal role in maintaining the mitochondrial quantity and quality control enabling the degradation of unwanted mitochondria, and thus rescues cellular homeostasis in response to stress. Accumulating evidence demonstrates that impaired mitophagy has been associated with many neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) in a variety of patients and disease models with neural death, oxidative stress and disturbed metabolism, either as the cause or consequence. These findings suggest that modulation of mitophagy may be considered as a valid therapeutic strategy in neurodegenerative diseases. In this review, we summarize recent findings on the mechanisms of mitophagy and its role in neurodegenerative diseases, with a particular focus on mitochondrial proteins acting as receptors that mediate mitophagy in these diseases.
线粒体功能障碍已被定义为与衰老相关疾病的特征之一，其特征是完整性受损、分布和大小异常、ATP 供应不足、ROS 产生增加，随后导致蛋白质、脂质和核酸受损和氧化。自噬是一种通过自噬有效清除受损或有缺陷的线粒体的方法，在维持线粒体数量和质量控制中起着关键作用，使不需要的线粒体降解，从而在应激时恢复细胞内稳态。越来越多的证据表明，受损的线粒体自噬与许多神经退行性疾病有关，如阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD）、肌萎缩侧索硬化症（ALS），在多种有神经死亡、氧化应激和代谢紊乱的患者和疾病模型中，无论是作为原因还是结果。这些发现表明，调节线粒体自噬可能被认为是神经退行性疾病的一种有效治疗策略。在这篇综述中，我们总结了线粒体自噬的机制及其在神经退行性疾病中的作用的最新发现，特别关注在这些疾病中作为介导线粒体自噬的受体的线粒体蛋白。
