Smirnova E, Shurland D L, Ryazantsev S N, van der Bliek A M
Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, California 90095-1737, USA.
J Cell Biol. 1998 Oct 19;143(2):351-8. doi: 10.1083/jcb.143.2.351.
Mitochondria exist as a dynamic tubular network with projections that move, break, and reseal in response to local environmental changes. We present evidence that a human dynamin-related protein (Drp1) is specifically required to establish this morphology. Drp1 is a GTPase with a domain structure similar to that of other dynamin family members. To identify the function of Drp1, we transiently transfected cells with mutant Drp1. A mutation in the GTPase domain caused profound alterations in mitochondrial morphology. The tubular projections normally present in wild-type cells were retracted into large perinuclear aggregates in cells expressing mutant Drp1. The morphology of other organelles was unaffected by mutant Drp1. There was also no effect of mutant Drp1 on the transport functions of the secretory and endocytic pathways. By EM, the mitochondrial aggregates found in cells that were transfected with mutant Drp1 appear as clusters of tubules rather than a large mass of coalescing membrane. We propose that Drp1 is important for distributing mitochondrial tubules throughout the cell. The function of this new dynamin-related protein in organelle morphology represents a novel role for a member of the dynamin family of proteins.
线粒体以动态管状网络的形式存在，其突起会根据局部环境变化移动、断裂并重新封闭。我们提供的证据表明，一种人类动力蛋白相关蛋白（Drp1）是建立这种形态所特别需要的。Drp1是一种GTP酶，其结构域结构与其他动力蛋白家族成员相似。为了确定Drp1的功能，我们用突变型Drp1瞬时转染细胞。GTP酶结构域中的突变导致线粒体形态发生深刻改变。野生型细胞中正常存在的管状突起在表达突变型Drp1的细胞中回缩成大的核周聚集体。其他细胞器的形态不受突变型Drp1的影响。突变型Drp1对分泌和内吞途径的运输功能也没有影响。通过电子显微镜观察，用突变型Drp1转染的细胞中发现的线粒体聚集体表现为成簇的小管，而不是大量融合的膜。我们认为Drp1对于线粒体小管在整个细胞中的分布很重要。这种新的动力蛋白相关蛋白在细胞器形态中的功能代表了动力蛋白家族成员的一种新作用。
