Parkin-induced mitophagy in the pathogenesis of Parkinson disease
Parkin-induced mitophagy in the pathogenesis of Parkinson disease
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DOI：
10.4161/auto.5.5.8505
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发表时间：
2009-07-01
期刊：
影响因子：
13.3
通讯作者：
Youle, Richard J.
中科院分区：
文献类型：
--
作者：
Narendra, Derek;Tanaka, Atsushi;Youle, Richard J.
敲除泛素连接酶Parkin，帕金森相关Park2的基因产物，导致果蝇线粒体完整性和功能的丧失。虽然Parkin主要存在于细胞质中，但我们发现Parkin被选择性地招募到具有低膜电位的功能失调线粒体中，并随后促进其自噬。在这里，我们报道了Parkin募集是电压依赖性的，不依赖于ATP或ph的变化。这些发现表明，Parkin促进线粒体膜电位丧失后功能失调线粒体的自噬，并暗示了帕金森病发病机制中线粒体的靶向消除。
Knockout of the ubiquitin ligase Parkin, the gene product of the Parkinson associated Park2, leads to loss of mitochondrial integrity and function in Drosophila melanogaster. Although Parkin is primarily cytosolic, we have found that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential and subsequently promotes their autophagy. Here we report that Parkin recruitment is voltage-dependent and independent of changes in ATP or pH. These findings suggest that Parkin promotes mitophagy of dysfunctional mitochondria following loss of mitochondrial membrane potential and implicates the targeted elimination of mitochondria in the pathogenesis of Parkinson disease.