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Miro (Mitochondrial Rho GTPase), a key player of Mitochondrial axonal transport and Mitochondrial dynamics in Neurodegenerative diseases
Mitochondrion ( IF 3.9 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.mito.2020.10.005
Komal Panchal , Anand Krishna Tiwari

Miro (mitochondrial Rho GTPases) a mitochondrial outer membrane protein, plays a vital role in the microtubule-based mitochondrial axonal transport, mitochondrial dynamics (fusion and fission) and Mito-Ca2+ homeostasis. It forms a major protein complex with Milton (an adaptor protein), kinesin and dynein (motor proteins), and facilitates bidirectional mitochondrial axonal transport such as anterograde and retrograde transport. By forming this protein complex, Miro facilitates the mitochondrial axonal transport and fulfills the neuronal energy demand, maintain the mitochondrial homeostasis and neuronal survival. It has been demonstrated that altered mitochondrial biogenesis, improper mitochondrial axonal transport, and mitochondrial dynamics are the early pathologies associated with most of the neurodegenerative diseases (NDs). Being the sole mitochondrial outer membrane protein associated with mitochondrial axonal transport-related processes, Miro proteins can be one of the key players in various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis(ALS) and Huntington's disease (HD). Thus, in the current review, we have discussed the evolutionarily conserved Miro proteins and its role in the pathogenesis of the various NDs. From this, we indicated that Miro proteins may act as a potential target for a novel therapeutic intervention for the treatment of various NDs.

中文翻译:

Miro(线粒体 Rho GTPase),神经退行性疾病中线粒体轴突运输和线粒体动力学的关键参与者

Miro(线粒体 Rho GTPases)是一种线粒体外膜蛋白,在基于微管的线粒体轴突运输、线粒体动力学(融合和裂变)和 Mito-Ca2+ 稳态中起着至关重要的作用。它与 Milton(一种衔接蛋白)、驱动蛋白和动力蛋白(运动蛋白)形成主要的蛋白质复合物,并促进双向线粒体轴突运输,如顺行和逆行运输。通过形成这种蛋白质复合物,Miro 促进线粒体轴突运输并满足神经元能量需求,维持线粒体稳态和神经元存活。已经证明,线粒体生物发生改变、线粒体轴突运输不当和线粒体动力学是与大多数神经退行性疾病 (ND) 相关的早期病理。作为与线粒体轴突转运相关过程相关的唯一线粒体外膜蛋白,Miro 蛋白可以成为各种 NDs 的关键参与者之一,如阿尔茨海默病 (AD)、帕金森病 (PD)、肌萎缩侧索硬化症 (ALS) 和亨廷顿舞蹈症疾病(HD)。因此,在当前的综述中,我们讨论了进化上保守的 Miro 蛋白及其在各种 ND 发病机制中的作用。由此,我们表明 Miro 蛋白可以作为治疗各种 ND 的新型治疗干预的潜在靶标。肌萎缩侧索硬化(ALS)和亨廷顿病(HD)。因此,在当前的综述中,我们讨论了进化上保守的 Miro 蛋白及其在各种 ND 发病机制中的作用。由此,我们表明 Miro 蛋白可以作为治疗各种 ND 的新型治疗干预的潜在靶标。肌萎缩侧索硬化(ALS)和亨廷顿病(HD)。因此,在当前的综述中,我们讨论了进化上保守的 Miro 蛋白及其在各种 ND 发病机制中的作用。由此,我们表明 Miro 蛋白可以作为治疗各种 ND 的新型治疗干预的潜在靶标。
更新日期:2021-01-01
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