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Parkin 介导的线粒体融合蛋白泛素化如何促进线粒体自噬?

How could Parkin-mediated ubiquitination of mitofusin promote mitophagy?

机构信息

MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.

出版信息

Autophagy. 2010 Jul;6(5):660-2. doi: 10.4161/auto.6.5.12242. Epub 2010 Jul 1.

Abstract

Much evidence links mitochondrial dysfunction to the death of neurons in Parkinson disease (PD), and is particularly emphasized by our growing understanding of the function of genes linked to recessively inherited PD such as PINK1, parkin and DJ-1. Recent work has revealed an exciting link between the PINK1-Parkin pathway and the autophagic turnover of dysfunctional mitochondrial (mitophagy). We have recently shown that mitofusin is ubiquitinated by Parkin when it is recruited to dysfunctional mitochondria. Recent work also shows that regulated fission and fusion events help segregate dysfunctional mitochondria prior to mitophagy. Here we hypothesize how Parkin-mediated ubiquitination of Mfn may play a role in this mechanism.

摘要

大量证据将线粒体功能障碍与帕金森病 (PD) 神经元死亡联系起来,而我们对与隐性遗传 PD 相关基因(如 PINK1、parkin 和 DJ-1)功能的理解的不断深入,尤其强调了这一点。最近的研究揭示了 PINK1-Parkin 途径与功能失调线粒体 (mitophagy) 的自噬性转化之间的令人兴奋的联系。我们最近表明,当 Parkin 招募到功能失调的线粒体时,它会使线粒体融合蛋白被泛素化。最近的工作还表明,调节的分裂和融合事件有助于在 mitophagy 之前将功能失调的线粒体隔离。在这里,我们假设 Parkin 介导的 Mfn 泛素化如何在这个机制中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62da/4196639/29f1875e8997/emss-51485-f0001.jpg

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