| Bcl-2家族蛋白调控线粒体膜通透性和细胞色素C释放的新机制 |
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| 引用本文： | 朱玉山,卢铁元,王蕊,黄理,马淇,赵丽霞,高平,雷晓波,倪碧云,林家凌,郝小江,陈佺. Bcl-2家族蛋白调控线粒体膜通透性和细胞色素C释放的新机制[J]. 生命科学, 2011, 0(11): 1076-1080 |
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| 作者姓名： | 朱玉山 卢铁元 王蕊 黄理 马淇 赵丽霞 高平 雷晓波 倪碧云 林家凌 郝小江 陈佺 |
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| 作者单位： | [1]南开大学生命科学学院药物化学生物学国家重点实验室,天津300071 [2]天津体育学院健康与运动系,天津300381 [3]中国科学院动物研究所生物膜与膜生物工程国家重点实验室,北京100101 [4]美国俄克拉荷马大学健康科学中心,诺曼56581 [5]中国科学院昆明植物研究所,昆明650204 |
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| 基金项目： | 国家自然科学基金国际合作项目（30910103910） |
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| 摘 要： | Bcl-2家族蛋白在调控线粒体功能和细胞色素C释放中起重要作用。最近发现Bcl-2分子通过与其他促凋亡分子相互作用调控线粒体外膜通透性,其具体分子机制尚不完全清楚。本课题组采用化学生物学方法,在研究Bax/Bak非依赖的细胞凋亡途径中,发现了一些小分子化合物能够诱导Bim表达量急剧升高,Bim能转位到线粒体上,与Bcl-2相互作用增强,并直接促进Bcl-2构象变化。有意义的是,Bim可以诱导Bcl-2功能发生转换并能够形成大的复合体通道来介导细胞色素C释放。研究结果提示Bcl-2分子可变成促凋亡分子,参与Bax/Bak非依赖的细胞色素C释放和细胞凋亡。
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| 关 键 词： | 线粒体 Bcl-2 细胞凋亡 细胞色素C |
Functional conversion of Bcl-2 into a pro-apoptotic molecule to regulate mitochondrial cytochrome c release |
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| ZHU Yu-Shan,LU Tie-Yuan,WANG Rui,HUANG Li,MA Qi,ZHAO Li-Xia,GAO Ping,LEI Xiao-Bo,NI Bi-Yun,LIN Jia-Ling,HAO Xiao-Jiang,CHEN. Functional conversion of Bcl-2 into a pro-apoptotic molecule to regulate mitochondrial cytochrome c release[J]. Chinese Bulletin of Life Sciences, 2011, 0(11): 1076-1080 |
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| Authors: | ZHU Yu-Shan LU Tie-Yuan WANG Rui HUANG Li MA Qi ZHAO Li-Xia GAO Ping LEI Xiao-Bo NI Bi-Yun LIN Jia-Ling HAO Xiao-Jiang CHEN |
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| Affiliation: | Quan,(1 State Key Laboratory of Medicinal Chemical Biology,School of Life Sciences,Nankai University,Tianjin 300071,China;2 Department of Health and Exercise Science,Tianjin University of Sport,Tianjin 300381,China;3 The State Key Laboratory of Biomembrane and Membrane Biotechnology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;4 Department of Biochemistry and Molecular Biology,University of Oklahoma Health Sciences Center,Oklahoma City,Oklahoma 73126,USA;5 The State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming 650204,China) |
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| Abstract: | Bcl-2 and its family proteins play pivotal roles in the regulation of the cytochrome c release and mitochondria functions.However,the mechanism on how Bcl-2 regulates mitochondrial outer membrane permeability is still not fully understood.We undertook a chemical biology approach to understand whether and how Bcl-2 regulates cytochrome c release in the absence of Bax and Bak.We identified several small compounds,such as gossypol,S-3 and PAO,that induced typical apoptosis in the bax/bak deficient cells.Mechanistic studies further revealed that these compounds are able to induce functional conversion of Bcl-2 into a Bax or Bak-like molecules.In particular,S-3 and PAO could induce the up-regulation of Bim which physically interacts with Bcl-2 at the MOM changing its conformation to form Bax-like pores which release cytochrome c and induce apoptosis.Since previous studies have generated overwhelming evidence showing that Bcl-2 is an anti-apoptotic molecule,it is surprising to find that Bim,a BH3-only protein and well known physiological inducer of apoptosis converts Bcl-2 to a Bax-like pro-apoptotic protein. |
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| Keywords: | mitochondria Bcl-2 apoptosis cytochrome c |
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