Mozdy A D, McCaffery J M, Shaw J M
Department of Biology, University of Utah, Salt Lake City, Utah 84112, USA.
J Cell Biol. 2000 Oct 16;151(2):367-80. doi: 10.1083/jcb.151.2.367.
Yeast Dnm1p is a soluble, dynamin-related GTPase that assembles on the outer mitochondrial membrane at sites where organelle division occurs. Although these Dnm1p-containing complexes are thought to trigger constriction and fission, little is known about their composition and assembly, and molecules required for their membrane recruitment have not been isolated. Using a genetic approach, we identified two new genes in the fission pathway, FIS1 and FIS2. FIS1 encodes a novel, outer mitochondrial membrane protein with its amino terminus exposed to the cytoplasm. Fis1p is the first integral membrane protein shown to participate in a eukaryotic membrane fission event. In a related study (Tieu, Q., and J. Nunnari. 2000. J. Cell Biol. 151:353-365), it was shown that the FIS2 gene product (called Mdv1p) colocalizes with Dnm1p on mitochondria. Genetic and morphological evidence indicate that Fis1p, but not Mdv1p, function is required for the proper assembly and distribution of Dnm1p-containing fission complexes on mitochondrial tubules. We propose that mitochondrial fission in yeast is a multi-step process, and that membrane-bound Fis1p is required for the proper assembly, membrane distribution, and function of Dnm1p-containing complexes during fission.
酵母Dnm1p是一种可溶性的、与发动蛋白相关的GTP酶，它在细胞器发生分裂的线粒体外膜上组装。尽管这些含有Dnm1p的复合物被认为会引发缢缩和裂变，但人们对它们的组成和组装知之甚少，而且尚未分离出其膜募集所需的分子。我们采用遗传学方法，在裂变途径中鉴定出两个新基因，即FIS1和FIS2。FIS1编码一种新的线粒体外膜蛋白，其氨基末端暴露于细胞质中。Fis1p是首个被证明参与真核细胞膜裂变事件的整合膜蛋白。在一项相关研究中（Tieu, Q.和J. Nunnari. 2000. J. Cell Biol. 151:353 - 365），研究表明FIS2基因产物（称为Mdv1p）与Dnm1p在线粒体上共定位。遗传学和形态学证据表明，Fis1p而非Mdv1p的功能是含Dnm1p的裂变复合物在线粒体小管上正确组装和分布所必需的。我们提出，酵母中的线粒体裂变是一个多步骤过程，并且膜结合的Fis1p是含Dnm1p的复合物在裂变过程中正确组装、膜分布和发挥功能所必需的。
