Impact of PINK1/Parkin-Mediated Mitophagy in the Development of Neurodegenerative Diseases
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摘要: 线粒体不仅是细胞能量代谢中枢，更参与信号转导及活性调控等重要生理过程。线粒体数量异常、mtDNA拷贝数失衡、基因突变累积以及自噬通路异常激活等现象会导致粒体功能障碍甚至细胞器功能障碍，还会激活细胞损伤和死亡的机制，从而导致各种疾病的发病。线粒体自噬作为高度特异性的自噬形式，在细胞器质量监控与稳态平衡中承担核心调控功能。以经典PINK1/Parkin通路介导的线粒体自噬作为切入点，总结线粒体自噬在神经退行性疾病中的作用及相关研究进展，为寻求靶向调控线粒体自噬改善神经退行性疾病的防治新策略提供新的思路。Abstract: Mitochondria not only serve as the central hub for cellular energy metabolism, but also participate in crucial physiological processes such as signal transduction and activity regulation. Abnormal mitochondrial quantity, imbalance in mtDNA copy number, accumulation of genetic mutations, and aberrant activation of autophagic pathways can lead to mitochondrial dysfunction or even organelle disorders, while activating mechanisms of cellular damage and death, consequently contributing to the pathogenesis of various diseases. As a highly selective form of autophagy, mitophagy plays a pivotal regulatory role in organelle quality control and homeostasis maintenance. This article focuses on the classic PINK1/Parkin pathway-mediated mitophagy as an entry point, summarizing recent research advances regarding the role of mitophagy in neurodegenerative diseases, aiming to provide novel insights for developing targeted mitophagy regulation strategies to improve prevention and treatment approaches for neurodegenerative disorders.
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Key words:
- Mitophagy /
- Oxidative stress /
- Parkinson's /
- Alzheimer's disease
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图 1 PINK1/Parkin通路介导的线粒体自噬
A：正常线粒体跨膜蛋白PARL蛋白酶切割处理PINK1；B：PINK1蛋白与Parkin介导的线粒体自噬模式图。
Figure 1. PINK1/Parkin pathway-mediated mitophagy
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