The WD-repeats of Net2p interact with Dnm1p and Fis1p to regulate division of mitochondria
The WD-repeats of Net2p interact with Dnm1p and Fis1p to regulate division of mitochondria
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DOI：
10.1091/mbc.e03-02-0092
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发表时间：
2003-10-01
影响因子：
3.3
通讯作者：
Jensen, RE
中科院分区：
文献类型：
--
作者：
Cerveny, KL;Jensen, RE
在酿酒酵母中，Net2、Fis1和Dnm1蛋白是线粒体分裂所必需的。Net2p有一个氨基末端区域，包含预测的卷曲螺旋基序和一个羧基末端区域，由WD-40重复序列组成。我们发现Net2p的氨基端部分与Fis1p相互作用，而羧基端区域与Dnm1p和Fis1p相互作用。在酵母细胞中，Net2p的任何一个结构域的过量产生都会毒害线粒体分裂，并且Net2p的wd重复引起的显性负作用被Dnm1p水平的增加所抑制。Net2p的wd区或Dnm1p的GTPase区的点突变破坏了正常的Net2p-Dnm1p相互作用，导致Net2p失去其正常的点状分布。我们的研究结果表明，Dnm1p与Net2p的wd重复序列相互作用，并以gtp依赖的方式将Net2p招募到线粒体分裂的位点。此外，我们的研究结果表明，Net2p是线粒体裂变成分正确组装以调节细胞器分裂所必需的。
The Net2, Fis1, and Dnm1 proteins are required for the division of mitochondria in the yeast Saccharomyces cerevisiae. Net2p has an amino-terminal region that contains predicted coiled-coil motifs and a carboxyl-terminal domain composed of WD-40 repeats. We found that the amino-terminal part of Net2p interacts with Fis1p, whereas the carboxyl-terminal region interacts with both Dnm1p and Fis1p. Overproduction of either domain of Net2p in yeast cells poisons mitochondrial fission, and the dominant-negative effect caused by the WD-repeats of Net2p is suppressed by increased levels of Dnm1p. Point mutations in the WD-region of Net2p or in the GTPase region of Dnm1p disrupt the normal Net2p-Dnm1p interaction, causing Net2p to lose its normal punctate distribution. Our results suggest that Dnm1p interacts with the WD-repeats of Net2p and in a GTP-dependent manner recruits Net2p to sites of mitochondrial division. Furthermore, our results indicate that Net2p is required for proper assembly of the mitochondrial fission components to regulate organelle division.