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利用 mt-Keima 评估线粒体自噬,揭示了 PINK1-Parkin 通路在诱导线粒体自噬中的重要作用。

Assessment of mitophagy in mt-Keima revealed an essential role of the PINK1-Parkin pathway in mitophagy induction .

机构信息

Peripheral Neuropathy Research Center, College of Medicine, Dong-A University, Busan, Korea.

Department of Biochemistry, College of Medicine, Dong-A University, Busan, Korea.

出版信息

FASEB J. 2019 Sep;33(9):9742-9751. doi: 10.1096/fj.201900073R. Epub 2019 May 23.

Abstract

Mitophagy has been implicated in mitochondrial quality control and in various human diseases. However, the study of mitophagy remains limited. We previously explored mitophagy using a transgenic mouse expressing the mitochondria-targeted fluorescent protein Keima (mt-Keima). Here, we generated mt-Keima to extend our efforts to study mitophagy . A series of experiments confirmed that mitophagy can be faithfully and quantitatively measured in mt-Keima . We also showed that alterations in mitophagy upon environmental and genetic perturbation can be measured in mt-Keima . Analysis of different tissues revealed a variation in basal mitophagy levels in tissues. In addition, we found a significant increase in mitophagy levels during embryogenesis. Importantly, loss-of-function genetic analysis demonstrated that the phosphatase and tensin homolog-induced putative kinase 1 (PINK1)-Parkin pathway is essential for the induction of mitophagy in response to hypoxic exposure and rotenone treatment. These studies showed that the mt-Keima system is a useful tool for understanding the role and molecular mechanism of mitophagy . In addition, we demonstrated the essential role of the PINK1-Parkin pathway in mitophagy induction in response to mitochondrial dysfunction.-Kim, Y. Y., Um, J.-H., Yoon, J.-H., Kim, H., Lee, D.-Y., Lee, Y. J., Jee, H. J., Kim, Y. M., Jang, J. S., Jang, Y.-G., Chung, J., Park, H. T., Finkel, T., Koh, H., Yun, J. Assessment of mitophagy in mt-Keima revealed an essential role of the PINK1-Parkin pathway in mitophagy induction .

摘要

自噬已被牵涉到线粒体的质量控制和各种人类疾病中。然而,对自噬的研究仍然有限。我们之前使用表达线粒体靶向荧光蛋白 Keima(mt-Keima)的转基因小鼠探索了自噬。在这里,我们生成了 mt-Keima 来扩展我们研究自噬的努力。一系列实验证实了 mt-Keima 中可以真实和定量地测量自噬。我们还表明,环境和遗传扰动时自噬的改变可以在 mt-Keima 中测量。对不同组织的分析显示了组织中基础自噬水平的变化。此外,我们发现胚胎发生过程中自噬水平显著增加。重要的是,功能丧失遗传分析表明,磷酸酶和张力蛋白同源诱导的假定激酶 1(PINK1)-Parkin 途径对于缺氧暴露和鱼藤酮处理时自噬的诱导是必需的。这些研究表明,mt-Keima 系统是理解自噬作用和分子机制的有用工具。此外,我们证明了 PINK1-Parkin 途径在响应线粒体功能障碍诱导自噬中的重要作用。-Kim,YY,Um,JH,Yoon,JH,Kim,HM,Lee,DY,Lee,YJ,Jee,HJ,Kim,YM,Jang,JS,Jang,YG,Chung,J,Park,HT,Finkel,T,Koh,H,Yun,J 在 mt-Keima 中评估自噬显示,PINK1-Parkin 途径在响应线粒体功能障碍诱导自噬中的作用至关重要。

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