Role of mitofusin 2 ( Mfn2) in controlling cellular proliferation
Role of mitofusin 2 ( Mfn2) in controlling cellular proliferation
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DOI：
10.1096/fj.13-230037
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发表时间：
2014-01-01
期刊：
影响因子：
4.8
通讯作者：
Longo, Dan L.
中科院分区：
文献类型：
--
作者：
Chen, Kuang-Hueih;Dasgupta, Asish;Longo, Dan L.
有报道称，Mitofusin2 （Mfn2）过表达时可抑制细胞增殖。我们想研究内源性Mfn2在细胞增殖中的作用，以及影响Mfn2线粒体定位和控制细胞增殖的结构特征。mfn2敲低的b细胞淋巴瘤细胞系BJAB克隆显示细胞增殖率增加。Mfn2基因敲除小鼠胚胎成纤维细胞（MEF）细胞的增殖能力也比对照野生型细胞增加了2倍，并且在重新引入Mfn2基因后，敲除的MEF细胞的增殖优势被阻断。Mfn2通过作为Ras的效应分子发挥抗增殖作用，从而抑制Ras- raf - erk信号通路。此外，Mfn2的n端（aa 1-264）和c端（aa 265-757）片段通过不同的机制抑制细胞增殖：n端介导的抑制是由于其与Raf-1的相互作用，而Mfn2的c端片段通过与Ras的相互作用抑制细胞增殖。n端片段对细胞增殖的抑制作用与其线粒体定位无关。总的来说，我们的数据为Mfn2在控制细胞增殖中的作用提供了新的见解。陈,K.-H。， Dasgupta， A, Ding， J, Indig， F. E, Ghosh， P., Longo， D. L. Mitofusin 2 （Mfn2）在细胞增殖调控中的作用。
It has been reported that Mitofusin2 (Mfn2) inhibits cell proliferation when overexpressed. We wanted to study the role of endogenous Mfn2 in cell proliferation, along with the structural features of Mfn2 that influence its mitochondrial localization and control of cell proliferation. Mfn2-knockdown clones of a B-cell lymphoma cell line BJAB exhibited an increased rate of cell proliferation. A 2-fold increase in cell proliferation was also observed in Mfn2-knockout mouse embryonic fibroblast (MEF) cells as compared with the control wild-type cells, and the proliferative advantage of the knockout MEF cells was blocked on reintroduction of the Mfn2 gene. Mfn2 exerts its antiproliferative effect by acting as an effector molecule of Ras, resulting in the inhibition of the Ras-Raf-ERK signaling pathway. Furthermore, both the N-terminal (aa 1-264) and the C-terminal (aa 265-757) fragments of Mfn2 blocked cell proliferation through distinct mechanisms: the N-terminal-mediated inhibition was due to its interaction with Raf-1, whereas the C-terminal fragment of Mfn2 inhibited cell proliferation by interacting with Ras. The inhibition of proliferation by the N-terminal fragment was independent of its mitochondrial localization. Collectively, our data provide new insights regarding the role of Mfn2 in controlling cellular proliferation.Chen, K.-H., Dasgupta, A., Ding, J., Indig, F. E., Ghosh, P., Longo, D. L. Role of Mitofusin 2 (Mfn2) in controlling cellular proliferation.