The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission.
The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission.
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DOI：
10.1083/jcb.200205031
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发表时间：
2002-08-05
期刊：
影响因子：
--
通讯作者：
Nunnari J
中科院分区：
文献类型：
--
作者：
Tieu Q;Okreglak V;Naylor K;Nunnari J
酵母线粒体分裂是一个多步骤的过程，在此过程中，动力蛋白相关的GTdR，Dnm 1 p，组装成点状结构，与线粒体外膜和介导线粒体分裂。Dnm 1 p依赖性分裂过程中的步骤受到WD重复蛋白Mdv 1 p和线粒体外膜蛋白Fis 1 p的作用的调节。我们以前的研究提出了一个模型，其中Mdv 1 p的功能是在Dnm 1 p组装步骤后调节裂变，Fis 1 p的功能是在两个不同的步骤，在早期，调节Dnm 1 p组装，后来，与Mdv 1 p一起，促进Dnm 1 p依赖的线粒体裂变。为了测试这个模型，我们研究了Mdv 1 p和Fis 1 p之间的物理和功能关系，目前的遗传，生化和双杂交数据表明，Fis 1 p-Mdv 1 p复合物是调节线粒体裂变所必需的。为了进一步确定Mdv 1 p在裂变中的作用，我们研究了Mdv 1 p与Dnm 1 p和Fis 1 p相互作用所需的结构特征。来自双杂交分析和GFP标记的Mdv 1 p结构域的数据表明，它包含两个功能不同的结构域，使其能够作为分子适配器来调节Dnm 1 p和Fis 1 p之间的顺序相互作用，并催化线粒体分裂中的限速步骤。
Yeast mitochondrial fission is a multistep process during which the dynamin-related GTPase, Dnm1p, assembles into punctate structures that associate with the outer mitochondrial membrane and mediate mitochondrial division. Steps in the Dnm1p-dependent process of fission are regulated by the actions of the WD repeat protein, Mdv1p, and the mitochondrial outer membrane protein, Fis1p. Our previous studies suggested a model where Mdv1p functions to regulate fission at a post-Dnm1p assembly step and Fis1p functions at two distinct steps, at an early point, to regulate Dnm1p assembly, and later, together with Mdv1p, to facilitate Dnm1p-dependent mitochondrial fission. To test this model, we have examined the physical and functional relationship between Mdv1p and Fis1p and present genetic, biochemical, and two-hybrid data indicating that a Fis1p–Mdv1p complex is required to regulate mitochondrial fission. To further define the role of Mdv1p in fission, we examined the structural features of Mdv1p required for its interactions with Dnm1p and Fis1p. Data from two-hybrid analyses and GFP-tagged domains of Mdv1p indicate that it contains two functionally distinct domains that enable it to function as a molecular adaptor to regulate sequential interactions between Dnm1p and Fis1p and catalyze a rate-limiting step in mitochondrial fission.
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