在酸性pH诱导膜结合后，Bcl-2的胞质结构域在模型线粒体外膜上形成小孔。
The cytosolic domain of Bcl-2 forms small pores in model mitochondrial outer membrane after acidic pH-induced membrane association.
作者信息
Peng Jun, Lapolla Suzanne M, Zhang Zhi, Lin Jialing
机构信息
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73190, USA.
出版信息
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2009 Feb;26(1):130-7.
The permeability of mitochondrial outer membrane (MOM) is regulated by the proteins of the Bcl-2 family via their interactions at the membrane. While pro-apoptotic Bax protein promotes MOM permeabilization (MOMP) releasing cytochrome c after activation by BH3-only protein, anti-apoptotic Bcl-2 protein protects MOM. However both Bax and Bcl-2 can form pores in model membranes. Unlike Bax pore that has been extensively studied and reported to be directly linked to MOMP, Bcl-2 pore is much less known; thus we investigated the pore-forming property of recombinant Bcl-2 lacking the C-terminal transmembrane sequence (Bcl-2deltaTM) in liposomal membranes of MOM lipids. We found that: (1) Bcl-2 formed pores at acidic pH that induced the association of Bcl-2 with liposome; (2) Bcl-2 pore size was dependent on Bcl-2 concentration, suggesting that oligomerization is involved in Bcl-2 pore formation; (3) Unlike Bax pore that could release large molecules up to 2 mega-Da, Bcl-2 pore was smaller and could only release the molecules of a few kilo-Da. Therefore, Bcl-2 and Bax may form different size pores in MOM, and while the large pore formed by Bax may release cytochrome c during apoptosis, the small pore formed by Bcl-2 may maintain the normal MOM permeability.
线粒体外膜（MOM）的通透性由Bcl-2家族蛋白通过它们在膜上的相互作用来调节。促凋亡的Bax蛋白在仅含BH3结构域的蛋白激活后促进线粒体外膜通透性改变（MOMP）并释放细胞色素c，而抗凋亡的Bcl-2蛋白则保护线粒体外膜。然而，Bax和Bcl-2都能在模型膜中形成孔道。与已被广泛研究且报道与MOMP直接相关的Bax孔道不同，Bcl-2孔道鲜为人知；因此，我们研究了缺乏C端跨膜序列的重组Bcl-2（Bcl-2deltaTM）在MOM脂质体膜中的成孔特性。我们发现：（1）Bcl-2在酸性pH下形成孔道，这诱导了Bcl-2与脂质体的结合；（2）Bcl-2孔道大小取决于Bcl-2浓度，表明寡聚化参与了Bcl-2孔道的形成；（3）与能释放高达2兆道尔顿大分子的Bax孔道不同，Bcl-2孔道较小，只能释放几千道尔顿的分子。因此，Bcl-2和Bax可能在MOM中形成不同大小的孔道，并且在细胞凋亡过程中，由Bax形成的大孔道可能释放细胞色素c，而由Bcl-2形成的小孔道可能维持MOM的正常通透性。
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