School of Medicine, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, LIGHT Building, Leeds, LS2 9JT, UK.
CNRS, Université de Paris, UPR 9080, Laboratoire de Biochimie Théorique, 13 Rue Pierre et Marie Curie, 75005, Paris, France.
J Membr Biol. 2019 Oct;252(4-5):293-306. doi: 10.1007/s00232-019-00089-y. Epub 2019 Sep 4.
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.
线粒体是具有动态特征的细胞器，其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外膜融合和裂变这两种持续力的结果。理解线粒体动力学的功能细节在生理学上是相关的，因为这种微妙平衡的干扰会产生关键的后果，并涉及到几种神经疾病。参与这个过程的分子因子是来自与动力蛋白相关的蛋白家族的大型 GTPases。它们催化核苷酸依赖性的膜重塑，并且从细菌到高等真核生物都广泛保守。尽管不同家族成员的结构特征有助于更详细地理解线粒体动力学的分子机制，但一些成员的完整结构以及功能寡聚体的精确组装在很大程度上仍然未知。随着越来越多的结构数据的出现，动力蛋白超家族的结构域模块性成为将知识转移到特征较少的成员的基础。在这篇综述中，我们首先将概述参与线粒体动力学的主要因子。然后，我们将讨论最近用于研究融合蛋白寡聚体的计算方法学的例子，并介绍如何将整合建模与生化数据一起使用，作为推进膜动力学这一仍然具有挑战性的领域的资产。
