Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Vic, Australia.
FEBS Lett. 2021 Apr;595(8):1184-1204. doi: 10.1002/1873-3468.14077. Epub 2021 Apr 5.
In animals, mitochondria are mainly organised into an interconnected tubular network extending across the cell along a cytoskeletal scaffold. Mitochondrial fission and fusion, as well as distribution along cytoskeletal tracks, are counterbalancing mechanisms acting in concert to maintain a mitochondrial network tuned to cellular function. Balanced mitochondrial dynamics permits quality control of the network including biogenesis and turnover, and distribution of mitochondrial DNA, and is linked to metabolic status. Cellular and organismal health relies on a delicate balance between fission and fusion, and large rearrangements in the mitochondrial network can be seen in response to cellular insults and disease. Indeed, dysfunction in the major components of the fission and fusion machineries including dynamin-related protein 1 (DRP1), mitofusins 1 and 2 (MFN1, MFN2) and optic atrophy protein 1 (OPA1) and ensuing imbalance of mitochondrial dynamics can lead to neurodegenerative disease. Altered mitochondrial dynamics is also seen in more common diseases. In this review, the machinery involved in mitochondrial dynamics and their dysfunction in disease will be discussed.
在动物中，线粒体主要组织成一个相互连接的管状网络，沿着细胞骨架延伸穿过细胞。线粒体的分裂和融合，以及沿着细胞骨架轨道的分布，是相互平衡的机制，协同作用以维持适应细胞功能的线粒体网络。平衡的线粒体动力学允许网络的质量控制，包括生物发生和周转，以及线粒体 DNA 的分布，并与代谢状态有关。细胞和机体的健康依赖于分裂和融合之间的微妙平衡，并且可以看到线粒体网络的大重排以响应细胞损伤和疾病。事实上，分裂和融合机械的主要成分（包括与 dynamin 相关蛋白 1（DRP1）、线粒体融合蛋白 1 和 2（MFN1、MFN2）和视神经萎缩蛋白 1（OPA1）以及随之而来的线粒体动力学失衡）的功能障碍可导致神经退行性疾病。在更常见的疾病中也可以看到改变的线粒体动力学。在这篇综述中，将讨论线粒体动力学的相关机制及其在疾病中的功能障碍。
