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A Molecular Perspective on Mitochondrial Membrane Fusion: From the Key Players to Oligomerization and Tethering of Mitofusin.
The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2019-09-04 , DOI: 10.1007/s00232-019-00089-y
Dario De Vecchis 1 , Astrid Brandner 2, 3 , Marc Baaden 2, 3 , Mickael M Cohen 3, 4 , Antoine Taly 2, 3
Affiliation  

Mitochondria are dynamic organelles characterized by an ultrastructural organization which is essential in maintaining their quality control and ensuring functional efficiency. The complex mitochondrial network is the result of the two ongoing forces of fusion and fission of inner and outer membranes. Understanding the functional details of mitochondrial dynamics is physiologically relevant as perturbations of this delicate equilibrium have critical consequences and involved in several neurological disorders. Molecular actors involved in this process are large GTPases from the dynamin-related protein family. They catalyze nucleotide-dependent membrane remodeling and are widely conserved from bacteria to higher eukaryotes. Although structural characterization of different family members has contributed in understanding molecular mechanisms of mitochondrial dynamics in more detail, the complete structure of some members as well as the precise assembly of functional oligomers remains largely unknown. As increasing structural data become available, the domain modularity across the dynamin superfamily emerged as a foundation for transfering the knowledge towards less characterized members. In this review, we will first provide an overview of the main actors involved in mitochondrial dynamics. We then discuss recent example of computational methodologies for the study of mitofusin oligomers, and present how the usage of integrative modeling in conjunction with biochemical data can be an asset in progressing the still challenging field of membrane dynamics.

中文翻译:

线粒体膜融合的分子视角:从关键参与者到线粒体融合素的寡聚和束缚。

线粒体是动态细胞器,其特征在于超微结构组织,对于维持其质量控制和确保功能效率至关重要。复杂的线粒体网络是内部和外部膜的两个持续融合和分裂力的结果。了解线粒体动力学的功能细节在生理上是相关的,因为这种微妙平衡的扰动会产生严重后果,并涉及多种神经系统疾病。参与此过程的分子参与者是来自与动力相关的蛋白质家族的大分子GTPases。它们催化核苷酸依赖性的膜重塑,并且从细菌到高级真核生物均被广泛保守。尽管不同家族成员的结构表征有助于更详细地了解线粒体动力学的分子机制,但某些成员的完整结构以及功能性低聚物的精确组装仍是未知之数。随着越来越多的结构数据变得可用,整个动态家族超域的模块性成为了将知识传递给特征较少的成员的基础。在这篇综述中,我们将首先概述与线粒体动力学有关的主要参与者。然后,我们讨论了用于研究丝裂霉素低聚物的计算方法的最新实例,并提出了如何将整合模型与生化数据结合起来使用如何在推进膜动力学仍然充满挑战的领域中成为一项资产。
更新日期:2019-11-01
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