Oligomeric BAX induces mitochondrial permeability transition and complete cytochrome c release without oxidative stress.
Oligomeric BAX induces mitochondrial permeability transition and complete cytochrome c release without oxidative stress.
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DOI：
10.1016/j.bbabio.2008.08.002
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发表时间：
2008-11
影响因子：
4.3
通讯作者：
Brustovetsky, Nickolay
中科院分区：
文献类型：
--
作者：
Li, Tsyregma;Brustovetsky, Tatiana;Antonsson, Bruno;Brustovetsky, Nickolay
在本研究中，我们研究了重组寡聚体Bax(BAXogo)诱导分离的脑线粒体释放细胞色素c的机制。我们发现BAXogo以浓度和时间依赖的方式引起细胞色素c的完全释放。这种释放类似于阿霉菌素诱导的释放，后者导致最大的线粒体肿胀，并消除OMM的屏障特性。通过光散射法和透射电子显微镜观察，BAXogo还产生了较大幅度的线粒体肿胀。此外，BAXogo还导致了线粒体的强烈去极化。三磷酸腺苷或环孢霉素A和ADP的联合应用可抑制BAXogo诱导的线粒体肿胀和去极化以及细胞色素c的释放，但不影响BAXogo插入OMM。用Amplex Red比色法测定线粒体H_2O_2释放量的结果表明，BAXogo和阿拉米星诱导的细胞色素c释放都伴随着ROS生成的抑制。MPT抑制剂可拮抗BAXogo对ROS生成的抑制，但不能拮抗甲氧西林对ROS的抑制作用。因此，BAXogo以MPT依赖的方式从分离的脑线粒体中完全释放细胞色素c，而不是通过需要线粒体重塑和OMM通透性的机制来参与氧化应激。
In the present study, we investigated the mechanism of cytochrome c release from isolated brain mitochondria induced by recombinant oligomeric BAX (BAXoligo). We found that BAXoligo caused a complete release of cytochrome c in a concentration- and time-dependent manner. The release was similar to those induced by alamethicin, which causes maximal mitochondrial swelling and eliminates barrier properties of the OMM. BAXoligo also produced large amplitude mitochondrial swelling as judged by light scattering assay and transmission electron microscopy. In addition, BAXoligo resulted in a strong mitochondrial depolarization. ATP or a combination of cyclosporin A and ADP, inhibitors of the mPT, suppressed BAXoligo-induced mitochondrial swelling and depolarization as well as cytochrome c release but did not influence BAXoligo insertion into the OMM. Both BAXoligo- and alamethicin-induced cytochrome c releases were accompanied by inhibition of ROS generation, which was assessed by measuring mitochondrial H2O2 release with an Amplex Red assay. The mPT inhibitors antagonized suppression of ROS generation caused by BAXoligo but not by alamethicin. Thus, BAXoligo resulted in a complete cytochrome c release from isolated brain mitochondria in the mPT-dependent manner without involvement of oxidative stress by the mechanism requiring mitochondrial remodeling and permeabilization of the OMM.
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影响因子：
5.3
作者：
Brustovetsky, N;Dubinsky, JM
通讯作者：
Dubinsky, JM
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
5.3
作者：
Eskes, R;Desagher, S;Martinou, JC
通讯作者：
Martinou, JC
影响因子：
3.5
作者：
Catisti, R;Vercesi, AE
通讯作者：
Vercesi, AE
影响因子：
4.8
作者：
Chauvin, C;De Oliveira, F;Fontaine, E
通讯作者：
Fontaine, E