Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases.
Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases.
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DOI：
10.1016/j.brainresrev.2010.11.004
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发表时间：
2011-06-24
影响因子：
--
通讯作者：
Mao P
中科院分区：
文献类型：
--
作者：
Reddy PH;Reddy TP;Manczak M;Calkins MJ;Shirendeb U;Mao P
本文就近年来神经退行性疾病（包括阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症）中线粒体动力学异常、线粒体断裂和神经元损伤的研究进展作一综述。GTdR家族蛋白质，包括分裂蛋白、动力蛋白相关蛋白1（Drp 1）、线粒体分裂蛋白1（Fis 1）和融合蛋白（Mfn 1、Mfn 2和Opa 1），对于维持线粒体分裂和融合平衡以及向神经元提供必需的三磷酸腺苷是必需的。其中，Drp 1参与线粒体的几个重要方面，包括形状，大小，分布，重塑和维持哺乳动物细胞中的X。此外，分子、细胞、电子显微镜和共聚焦成像研究的最新进展表明，Drp 1与几种细胞功能相关，包括线粒体和过氧化物酶体片段化、磷酸化、SUMO化、泛素化和细胞死亡。在过去的二十年里，在酵母、蠕虫和哺乳动物细胞中研究线粒体动力学方面取得了巨大进展;这项研究提供了将Drp 1与神经退行性疾病联系起来的证据。神经退行性疾病领域的研究人员开始认识到Drp 1可能参与引起神经退行性疾病中的线粒体片段化和异常线粒体动力学。本文总结了酵母、蠕虫和哺乳动物中Drp 1与线粒体分裂和融合相关的研究结果。基于Reddy实验室和其他人的研究结果，我们提出神经退行性疾病（包括AD，PD，HD和ALS）的突变蛋白与Drp 1相互作用，激活线粒体分裂机制，过度片段化线粒体，并损害线粒体转运和线粒体动力学，最终导致线粒体功能障碍和神经元损伤。
The purpose of this article is to review the recent developments of abnormal mitochondrial dynamics, mitochondrial fragmentation, and neuronal damage in neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. The GTPase family of proteins, including fission proteins, dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1), and fusion proteins (Mfn1, Mfn2 and Opa1) are essential to maintain mitochondrial fission and fusion balance, and to provide necessary adenosine triphosphate to neurons. Among these, Drp1 is involved in several important aspects of mitochondria, including shape, size, distribution, remodeling, and maintenance of X in mammalian cells. In addition, recent advancements in molecular, cellular, electron microscopy, and confocal imaging studies revealed that Drp1 is associated with several cellular functions, including mitochondrial and peroxisomal fragmentation, phosphorylation, SUMOylation, ubiquitination, and cell death. In the last two decades, tremendous progress has been made in researching mitochondrial dynamics, in yeast, worms, and mammalian cells; and this research has provided evidence linking Drp1 to neurodegenerative diseases. Researchers in the neurodegenerative disease field are beginning to recognize the possible involvement of Drp1 in causing mitochondrial fragmentation and abnormal mitochondrial dynamics in neurodegenerative diseases. This article summarizes research findings relating Drp1 to mitochondrial fission and fusion, in yeast, worms, and mammals. Based on findings from the Reddy laboratory and others’, we propose that mutant proteins of neurodegenerative diseases, including AD, PD, HD, and ALS, interact with Drp1, activate mitochondrial fission machinery, fragment mitochondria excessively, and impair mitochondrial transport and mitochondrial dynamics, ultimately causing mitochondrial dysfunction and neuronal damage.
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