细胞质切割的 PINK1 抑制 Parkin 向线粒体的易位和线粒体自噬。
Cytosolic cleaved PINK1 represses Parkin translocation to mitochondria and mitophagy.
机构信息
Center for Motor Neuron Biology and Disease and the Columbia Translational Neuroscience Initiative, Columbia University, New York, NY, USA.
出版信息
EMBO Rep. 2014 Jan;15(1):86-93. doi: 10.1002/embr.201337294. Epub 2013 Dec 15.
Abstract
PINK1 is a mitochondrial kinase proposed to have a role in the pathogenesis of Parkinson's disease through the regulation of mitophagy. Here, we show that the PINK1 main cleavage product, PINK152, after being generated inside mitochondria, can exit these organelles and localize to the cytosol, where it is not only destined for degradation by the proteasome but binds to Parkin. The interaction of cytosolic PINK1 with Parkin represses Parkin translocation to the mitochondria and subsequent mitophagy. Our work therefore highlights the existence of two cellular pools of PINK1 that have different effects on Parkin translocation and mitophagy.
摘要
PINK1 是一种线粒体激酶，被认为通过调节线粒体自噬在帕金森病的发病机制中起作用。在这里，我们表明 PINK1 的主要切割产物 PINK152 在在线粒体内部生成后，可以离开这些细胞器并定位于细胞质，在那里它不仅注定要被蛋白酶体降解，而且还与 Parkin 结合。细胞质中的 PINK1 与 Parkin 的相互作用抑制 Parkin 向线粒体的易位和随后的线粒体自噬。因此，我们的工作强调了 PINK1 存在两种细胞池，它们对 Parkin 易位和线粒体自噬有不同的影响。
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