Mitochondrial trafficking of APP and alpha synuclein: Relevance to mitochondrial dysfunction in Alzheimer's and Parkinson's diseases.
Mitochondrial trafficking of APP and alpha synuclein: Relevance to mitochondrial dysfunction in Alzheimer's and Parkinson's diseases.
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DOI：
10.1016/j.bbadis.2009.07.007
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发表时间：
2010-01
影响因子：
6.2
通讯作者：
Anandatheerthavarada, Hindupur K.
中科院分区：
文献类型：
--
作者：
Devi, Latha;Anandatheerthavarada, Hindupur K.
关键词：
线粒体功能障碍是与包括神经退行性疾病在内的多种疾病相关的重要细胞内病变。除了衰老、氧化应激和线粒体DNA突变之外，最近的研究还暗示了蛋白质如质膜相关淀粉样前体蛋白（APP）和细胞溶质α突触核蛋白的线粒体积累分别在阿尔茨海默病（AD）和帕金森病（PD）的线粒体功能障碍的发病机制中的作用。这两种蛋白质都含有神秘的线粒体靶向信号，这些信号驱动它们在线粒体中的转运。一般来说，核编码蛋白质进入线粒体是由位于线粒体外膜和内膜中的输入受体辅助的。越来越多的证据表明，APP和α-synclein与输入受体相互作用，以进入线粒体区室。此外，APP的羧基末端切割产物，104 kDa Abeta也在线粒体外膜输入受体的帮助下被转运到线粒体中。本文综述了这两种结构不同的蛋白质在线粒体中的靶向和积累作用，以及它们影响线粒体生理功能的机制模式
Mitochondrial dysfunction is an important intracellular lesion associated with a wide variety of diseases including neurodegenerative disorders. In addition to aging, oxidative stress and mitochondrial DNA mutations, recent studies have implicated a role for the mitochondrial accumulation of proteins such as plasma membrane associated amyloid precursor protein (APP) and cytosolic alpha synuclein in the pathogenesis of mitochondrial dysfunction in Alzheimer’s disease (AD) and Parkinson’s disease (PD), respectively. Both of these proteins contain cryptic mitochondrial targeting signals, which drive their transport across mitochondria. In general, mitochondrial entry of nuclear coded proteins is assisted by import receptors situated in both outer and inner mitochondrial membranes. A growing number of evidence suggests that APP and alpha synclein interact with import receptors to gain entry into mitochondrial compartment. Additionally, carboxy terminal cleaved product of APP, ∼ 4kDa Abeta, is also transported into mitochondria with the help of mitochondrial outer membrane import receptors. This review focuses on the mitochondrial targeting and accumulation of these two structurally different proteins and the mode of mechanism by which they affect the physiological functions of mitochondria
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DOI：
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发表时间：
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