Changes in specific lipids regulate BAX‐induced mitochondrial permeability transition
Changes in specific lipids regulate BAX‐induced mitochondrial permeability transition
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特定脂质的变化调节 BAX 诱导的线粒体通透性转变
DOI：
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
C. Zazueta
中科院分区：
文献类型：
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作者：
E. Martínez;N. García;F. Correa;M. Franco;C. Zazueta
最近的证据表明线粒体中存在脂质微区，显然作为结构元件与一些线粒体渗透性转换成孔蛋白和Bcl-2家族成员共存。本研究的目的是研究膜微区的主要成分（例如胆固醇和鞘脂）在重组BAX（rBAX）激活线粒体通透性转换孔（mPTP）中的相关性。为此目的，我们使用化学修饰的肾皮质线粒体和甲状腺功能减退大鼠的肾皮质线粒体，其显示出体内修饰的线粒体脂质组成。 寡聚体rBAX诱导增强的渗透性构象的mPTP的控制线粒体。当用螯合剂甲基-β-环糊精修饰线粒体的胆固醇和神经节苷脂含量时，rBAX未能诱导mPTP开放。因此，甲状腺功能减退的线粒体，与内源性较低的胆固醇和神经节苷脂含量，表现出抵抗mPTP开放诱导的rBAX。这些观察结果表明，丰富的胆固醇和神经节苷脂结构域的线粒体膜可能决定BAX与mPTP的相互作用。一个有趣的观察结果是，在对照线粒体中化学提取胆固醇和神经节苷脂对rBAX插入没有影响。相反，在甲状腺功能减退的线粒体中，与对照线粒体相比，rBAX插入显着减少。膜和蛋白质的变化与甲状腺的状态和它们可能的作用rBAX对接到膜进行了讨论。
Recent evidence suggests the existence of lipid microdomains in mitochondria, apparently coexisting as structural elements with some of the mitochondrial permeability transition pore‐forming proteins and members of the Bcl‐2 family. The aim of this study was to investigate the relevance of the main components of membrane microdomains (e.g. cholesterol and sphingolipids) in activation of the mitochondrial permeability transition pore (mPTP) by recombinant BAX (rBAX). For this purpose, we used chemically modified renal cortex mitochondria and renal cortex mitochondria from hypothyroid rats that show a modified mitochondrial lipid composition in vivo. Oligomeric rBAX induced an enhanced permeability conformation in the mPTP of control mitochondria. rBAX failed to induce mPTP opening when the cholesterol and ganglioside content of mitochondria were modified with the chelator methyl‐beta‐cyclodextrin. Accordingly, hypothyroid mitochondria, with endogenously lower cholesterol and ganglioside content, showed resistance to mPTP opening induced by rBAX. These observations suggest that enriched cholesterol and ganglioside domains in the mitochondrial membranes may determine BAX interaction with the mPTP. An intriguing observation was that chemical extraction of cholesterol and ganglioside in control mitochondria did not have an effect on rBAX insertion. Conversely, in hypothyroid mitochondria, rBAX insertion was diminished dramatically compared with control mitochondria. The membrane and protein changes associated with thyroid status and their possible role in rBAX docking into the membranes are discussed.
高效液相色谱法测定 2,4-二硝基苯酰肼形式的神经节苷脂。
DOI：
10.1042/bj2350755
发表时间：
1986
期刊：
The Biochemical journal
影响因子：
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作者：
Miyazaki,K;Okamura,N;Kishimoto,Y;Lee,YC
通讯作者：
Lee,YC
DOI：
10.1074/jbc.271.7.3684
发表时间：
1996-02
期刊：
The Journal of biological chemistry
影响因子：
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作者：
J. Nakayama;M. Fukuda;Y. Hirabayashi;A. Kanamori;K. Sasaki;T. Nishi;M. Fukuda
通讯作者：
J. Nakayama;M. Fukuda;Y. Hirabayashi;A. Kanamori;K. Sasaki;T. Nishi;M. Fukuda