Mitofusins as mitochondrial anchors and tethers
Mitofusins as mitochondrial anchors and tethers
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DOI：
10.1016/j.yjmcc.2020.04.016
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发表时间：
2020-05-01
影响因子：
5
通讯作者：
Dorn, Gerald W., II
中科院分区：
文献类型：
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作者：
Dorn, Gerald W., II
线粒体有自己的基因组和议事日程。就像它们的原始细菌祖先一样，线粒体与它们的环境和细胞器同事在它们的物理界面，即线粒体外膜上相互作用。在外膜蛋白中，有丝分裂蛋白（MFN）越来越被认为是线粒体-线粒体和线粒体-网状相互作用的仲裁者。本文综述了MFN1和MFN2在心脏和其他器官中的作用，它们是将线粒体相互连接或与其他细胞器连接的蛋白质，也是各种大分子复合物的线粒体锚定蛋白。本文综述了mfn介导的系固和锚定对线粒体融合、运动、线粒体自噬和线粒体-内质网钙串扰的影响。从有丝分裂蛋白作为拴系和锚定蛋白的共同功能的角度探讨病理生理意义，而不是作为单个过程的介质。最后，对于为什么小鼠MFN基因敲除研究显示出严重的多系统表型，而与MFN突变相关的罕见人类疾病的范围有限，提出了一些有根据的推测。
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.