The role of Fis1p-Mdv1p interactions in mitochondrial fission complex assembly
The role of Fis1p-Mdv1p interactions in mitochondrial fission complex assembly
复制标题
DOI：
10.1083/jcb.200506158
复制
发表时间：
2005-10-24
影响因子：
7.8
通讯作者：
Shaw, JM
中科院分区：
文献类型：
--
作者：
Karren, MA;Coonrod, EM;Shaw, JM
线粒体分裂需要 Fis1p、Mdv1p 和 Dnm1p GTPase 之间的协调相互作用，它们在线粒体外膜上组装成裂变复合物。完整的外膜蛋白 Fis1p 包含一个由四肽重复 (TPR) 样折叠和短 NH2 末端螺旋组成的胞质结构域。尽管已知细胞质结构域对于 Mdv1p 和 Dnm1p 组装成裂变复合物是必需的，但这种组装的分子细节尚不清楚。在这项研究中，我们提供了新的证据证明 Fis1p-Mdv1p 相互作用是直接的。此外，我们发现 Fis1p TPR 样结构域中的条件突变会导致裂变复合物组装缺陷，而这种缺陷会被 Mdv1p 预测的卷曲线圈中的突变所抑制。我们还定义了 Fis1p NH2 末端臂和 TPR 样折叠的可分离功能。这些研究表明，Fis1p TPR 样折叠的凹形结合表面在线粒体裂变过程中与 Mdv1p 相互作用，并且 Mdv1p 促进 Dnm1p 招募到功能性裂变复合物中。
Mitochondrial division requires coordinated interactions among Fis1p, Mdv1p, and the Dnm1p GTPase, which assemble into fission complexes on the outer mitochondrial membrane. The integral outer membrane protein Fis1p contains a cytoplasmic domain consisting of a tetratricopeptide repeat (TPR)-like fold and a short NH2-terminal helix. Although it is known that the cytoplasmic domain is necessary for assembly of Mdv1p and Dnm1p into fission complexes, the molecular details of this assembly are not clear. In this study, we provide new evidence that the Fis1p-Mdv1p interaction is direct. Furthermore, we show that conditional mutations in the Fis1p TPR-like domain cause fission complex assembly defects that are suppressed by mutations in the Mdv1p-predicted coiled coil. We also define separable functions for the Fis1p NH2-terminal arm and TPR-like fold. These studies suggest that the concave binding surface of the Fis1p TPR-like fold interacts with Mdv1p during mitochondrial fission and that Mdv1p facilitates Dnm1p recruitment into functional fission complexes.