Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892, USA.
BMC Biol. 2018 Jan 10;16(1):2. doi: 10.1186/s12915-017-0470-7.
Insights from inherited forms of parkinsonism suggest that insufficient mitophagy may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps maintain a healthy mitochondrial network, is initiated by activation of the PINK1 kinase specifically on damaged mitochondria. Recent investigation of this process reveals that import of PINK1 into mitochondria is regulated and yields a stress-sensing mechanism. In this review, we focus on the mechanisms of mitochondrial stress-dependent PINK1 activation that is exerted by regulated import of PINK1 into different mitochondrial compartments and how this offers strategies to pharmacologically activate the PINK1/Parkin pathway.
从遗传性帕金森病中得到的启示表明，线粒体自噬不足可能是这种疾病的一个病因。PINK1/Parkin 依赖性的线粒体自噬有助于维持健康的线粒体网络，它是由 PINK1 激酶在受损的线粒体上特异性激活而引发的。最近对这一过程的研究揭示，PINK1 向线粒体的输入受到调控，并产生了一种应激感应机制。在这篇综述中，我们重点介绍了线粒体应激依赖性 PINK1 激活的机制，这种机制是通过 PINK1 向不同的线粒体区室的调控性输入来实现的，以及这如何为药理学激活 PINK1/Parkin 途径提供了策略。
