Dynamin-related protein Drp1 is required for Bax translocation to mitochondria in response to irradiation-induced apoptosis
Dynamin-related protein Drp1 is required for Bax translocation to mitochondria in response to irradiation-induced apoptosis
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Dynamin 相关蛋白 Drp1 是 Bax 易位至线粒体以响应辐射诱导的细胞凋亡所必需的
DOI：
10.18632/oncotarget.4200
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发表时间：
2015-09-08
期刊：
影响因子：
--
通讯作者：
Liu, Feng-Ting
中科院分区：
文献类型：
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作者：
Wang, Ping;Wang, Peiguo;Liu, Feng-Ting
促凋亡蛋白Bax从细胞质到线粒体的易位是DNA损伤介导的细胞凋亡中的关键步骤，并且也被发现参与线粒体片段化。辐射诱导的细胞色素c释放和细胞凋亡与Bax激活有关，但与线粒体碎片无关。Bax和Drp1易位从细胞质到线粒体的辐射响应。然而，Drp1线粒体易位和寡聚化并不需要Bax，并且未能诱导Bax缺陷型弥漫性大B细胞淋巴瘤（DLBCL）细胞的凋亡。使用荧光显微镜和强度相关性分析，我们表明，Bax和Drp1共定位和水平的共定位增加紫外线照射。使用共免疫沉淀，我们证实Bax和Drp1是结合伴侣。辐射诱导的活性Bax和Drp1之间的相互作用的时间相关的增加。利用siRNA敲除Drp1可阻断紫外线照射介导的Bax线粒体易位。总之，我们的研究结果首次表明，Drp1是Bax线粒体易位所必需的，但单独的Drp1诱导的线粒体片段化不足以诱导DLBCL细胞的凋亡。
Translocation of the pro-apoptotic protein Bax from the cytosol to the mitochondria is a crucial step in DNA damage-mediated apoptosis, and is also found to be involved in mitochondrial fragmentation. Irradiation-induced cytochrome c release and apoptosis was associated with Bax activation, but not mitochondrial fragmentation. Both Bax and Drp1 translocated from the cytosol to the mitochondria in response to irradiation. However, Drp1 mitochondrial translocation and oligomerization did not require Bax, and failed to induce apoptosis in Bax deficient diffuse large B-cell lymphoma (DLBCL) cells. Using fluorescent microscopy and the intensity correlation analysis, we demonstrated that Bax and Drp1 were colocalized and the levels of colocalization were increased by UV irradiation. Using co-immuno-precipitation, we confirmed that Bax and Drp1 were binding partners. Irradiation induced a time-associated increase in the interaction between active Bax and Drp1. Knocking down Drp1 using siRNA blocked UV irradiation-mediated Bax mitochondrial translocation. In conclusion, our findings demonstrate for the first time, that Drp1 is required for Bax mitochondrial translocation, but Drp1-induced mitochondrial fragmentation alone is not sufficient to induce apoptosis in DLBCL cells.