Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
J Mol Cell Cardiol. 2020 May;142:146-153. doi: 10.1016/j.yjmcc.2020.04.016. Epub 2020 Apr 15.
Mitochondria have their own genomes and their own agendas. Like their primitive bacterial ancestors, mitochondria interact with their environment and organelle colleagues at their physical interfaces, the outer mitochondrial membrane. Among outer membrane proteins, mitofusins (MFN) are increasingly recognized for their roles as arbiters of mitochondria-mitochondria and mitochondria-reticular interactions. This review examines the roles of MFN1 and MFN2 in the heart and other organs as proteins that tether mitochondria to each other or to other organelles, and as mitochondrial anchoring proteins for various macromolecular complexes. The consequences of MFN-mediated tethering and anchoring on mitochondrial fusion, motility, mitophagy, and mitochondria-ER calcium cross-talk are reviewed. Pathophysiological implications are explored from the perspective of mitofusin common functioning as tethering and anchoring proteins, rather than as mediators of individual processes. Finally, some informed speculation is provided for why mouse MFN knockout studies show severe multi-system phenotypes whereas rare human diseases linked to MFN mutations are limited in scope.
线粒体有自己的基因组和议程。像它们原始的细菌祖先一样，线粒体在其物理界面——外膜上与环境和细胞器同事相互作用。在外膜蛋白中，越来越多的人认识到它们在调节线粒体-线粒体和线粒体-网状结构相互作用方面的作用。本综述探讨了 MFN1 和 MFN2 在心脏和其他器官中的作用，作为将线粒体彼此连接或与其他细胞器连接的蛋白质，以及作为各种大分子复合物的线粒体锚定蛋白。还综述了 MFN 介导的连接和锚定对线粒体融合、运动、线粒体自噬和线粒体-内质网钙交叉对话的影响。从作为连接和锚定蛋白而不是作为单个过程的调节剂的角度探讨了病理生理学意义。最后，针对为什么 MFN 敲除小鼠研究显示出严重的多系统表型，而与 MFN 突变相关的人类罕见疾病范围有限，提供了一些有根据的推测。
