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Mff 是哺乳动物细胞中线粒体分裂过程中 Drp1 招募到线粒体所必需的因素。

Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells.

机构信息

Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.

出版信息

J Cell Biol. 2010 Dec 13;191(6):1141-58. doi: 10.1083/jcb.201007152.

DOI:10.1083/jcb.201007152
PMID:21149567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3002033/
Abstract

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.

摘要

细胞质动力相关鸟苷三磷酸酶 Drp1 被招募到线粒体并介导线粒体裂变。虽然线粒体外膜 (MOM) 蛋白 Fis1 被认为是 Drp1 的受体，但这尚未得到证实。为了分析 Drp1 募集的机制，我们操纵了线粒体分裂和融合蛋白的表达，并证明了 (a) 线粒体分裂因子 (Mff) 的敲低将 Drp1 焦点从 MOM 上释放出来，同时伴随着网络延伸，而 Mff 的过表达刺激了 Drp1 对线粒体的募集，同时伴随着线粒体裂变；(b) Mff 依赖性线粒体裂变独立于 Fis1 进行；(c) 具有质膜靶向 CAAX 基序的 Mff 突变体将 Drp1 引导至靶膜；(d) Mff 和 Drp1 在体外和体内相互作用；(e) 敲低 Drp1 和 Mff 但不敲低 Fis1 会影响外源性刺激诱导的线粒体裂变和细胞凋亡；以及 (f) 在结肠癌细胞中条件性敲除 Fis1 表明它对于线粒体裂变不是必需的。因此，Mff 作为 Drp1 在线粒体募集中的必需因子发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/64795f020b77/JCB_201007152_GS_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/798b412d9806/JCB_201007152_RGB_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/a589a814af5f/JCB_201007152_RGB_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/5522e18400eb/JCB_201007152R_RGB_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/330f7ec22d5d/JCB_201007152_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/ca6fb5108514/JCB_201007152_RGB_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/0af79d96b47b/JCB_201007152R_GS_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/154dee3521d0/JCB_201007152_RGB_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/a09c529fe21a/JCB_201007152_RGB_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/43951fe7069c/JCB_201007152_RGB_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/64795f020b77/JCB_201007152_GS_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/798b412d9806/JCB_201007152_RGB_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/a589a814af5f/JCB_201007152_RGB_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/5522e18400eb/JCB_201007152R_RGB_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/330f7ec22d5d/JCB_201007152_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/ca6fb5108514/JCB_201007152_RGB_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/0af79d96b47b/JCB_201007152R_GS_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/154dee3521d0/JCB_201007152_RGB_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/a09c529fe21a/JCB_201007152_RGB_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/43951fe7069c/JCB_201007152_RGB_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0012/3002033/64795f020b77/JCB_201007152_GS_Fig10.jpg

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