Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells.
Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells.
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DOI：
10.1083/jcb.201007152
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发表时间：
2010-12-13
期刊：
影响因子：
--
通讯作者：
Mihara K
中科院分区：
文献类型：
--
作者：
Otera H;Wang C;Cleland MM;Setoguchi K;Yokota S;Youle RJ;Mihara K
动力蛋白相关的GTdR Drp 1定位于线粒体依赖于线粒体分裂因子Mff。细胞质动力蛋白相关的鸟苷三磷酸酶Drp 1被募集到线粒体并介导线粒体分裂。虽然线粒体外膜蛋白Fis 1被认为是Drp 1受体，但尚未得到证实。为了分析Drp 1募集的机制，我们操纵了线粒体分裂和融合蛋白的表达，并证明：（a）线粒体分裂因子（Mff）敲低使Drp 1从线粒体中释放出来，并伴随着网络的延伸，而Mff过表达则刺激线粒体募集Drp 1，并伴随着线粒体分裂;（B）Mff依赖的线粒体分裂独立于Fis 1进行;（c）具有质膜靶向CAAX基序的Mff突变体将Drp 1引导至靶膜;（d）Mff和Drp 1在体外和体内物理相互作用;（e）外源刺激诱导的线粒体分裂和凋亡受到Drp 1和Mff而不是Fis 1的敲低的损害;和（f）结肠癌细胞中Fis 1的条件性敲除揭示了它对于线粒体分裂是不利的。因此，Mff作为线粒体募集Drp 1的重要因子发挥作用。
Localization of the dynamin-related GTPase Drp1 to mitochondria relies on the mitochondrial fission factor Mff. The cytoplasmic dynamin-related guanosine triphosphatase Drp1 is recruited to mitochondria and mediates mitochondrial fission. Although the mitochondrial outer membrane (MOM) protein Fis1 is thought to be a Drp1 receptor, this has not been confirmed. To analyze the mechanism of Drp1 recruitment, we manipulated the expression of mitochondrial fission and fusion proteins and demonstrated that (a) mitochondrial fission factor (Mff) knockdown released the Drp1 foci from the MOM accompanied by network extension, whereas Mff overexpression stimulated mitochondrial recruitment of Drp1 accompanied by mitochondrial fission; (b) Mff-dependent mitochondrial fission proceeded independent of Fis1; (c) a Mff mutant with the plasma membrane–targeted CAAX motif directed Drp1 to the target membrane; (d) Mff and Drp1 physically interacted in vitro and in vivo; (e) exogenous stimuli–induced mitochondrial fission and apoptosis were compromised by knockdown of Drp1 and Mff but not Fis1; and (f) conditional knockout of Fis1 in colon carcinoma cells revealed that it is dispensable for mitochondrial fission. Thus, Mff functions as an essential factor in mitochondrial recruitment of Drp1.
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影响因子：
9.2
作者：
De Vos, KJ;Allan, VJ;Sheetz, MP
通讯作者：
Sheetz, MP
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
4.8
作者：
Chang, Chuang-Rung;Manlandro, Cara Marie;Blackstone, Craig
通讯作者：
Blackstone, Craig
影响因子：
11.8
作者：
Cerveny, Kara L.;Studer, Seth L.;Sesaki, Hiromi
通讯作者：
Sesaki, Hiromi
DOI：
10.1073/pnas.0604602103
发表时间：
2006-09-19
影响因子：
11.1
作者：
Egger, Gerda;Jeong, Shinwu;Liang, Gangning
通讯作者：
Liang, Gangning