Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties, permeabilization and cell death.
Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties, permeabilization and cell death.
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DOI：
10.1016/j.bbabio.2010.02.010
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发表时间：
2010-06
影响因子：
4.3
通讯作者：
Fernandez-Checa, Jose C.
中科院分区：
文献类型：
--
作者：
Montero, Joan;Mari, Montserrat;Colell, Anna;Morales, Albert;Basanez, Gorka;Garcia-Ruiz, Carmen;Fernandez-Checa, Jose C.
已知线粒体主动调节细胞死亡，死亡的最终表型由细胞的代谢和能量状态决定。线粒体膜通透性(线粒体膜通透性)是细胞死亡中的一个关键事件，因为它调节线粒体功能障碍的程度和膜间蛋白的释放，这些蛋白在caspase的激活和组装中发挥作用。除了Bcl-2家族中促凋亡成员的关键作用外，线粒体膜的脂质成分也越来越被认为是调节基质金属蛋白酶，从而调节细胞死亡的重要因素。胆固醇在线粒体膜上的非生理性积聚调节线粒体膜的物理性质，在Bax和死亡配体诱导的细胞死亡过程中，依赖于线粒体GSH(MGSH)的水平，促进或损害线粒体膜的线粒体膜上的线粒体膜，进而调节心磷脂的氧化状态。胆固醇介导的mGSH耗竭刺激了肿瘤坏死因子诱导的活性氧和随后的心磷脂过氧化，从而破坏了脂双层的稳定性，并增强了Bax诱导的膜通透性。这些数据表明，线粒体胆固醇和过氧化心磷脂的平衡调节线粒体膜的特性和通透性，在细胞死亡中起到变阻器的作用。
Mitochondria are known to actively regulate cell death with the final phenotype of demise being determined by the metabolic and energetic status of the cell. Mitochondrial membrane permeabilization (MMP) is a critical event in cell death, as it regulates the degree of mitochondrial dysfunction and the release of intermembrane proteins that function in the activation and assembly of caspases. In addition to the crucial role of proapoptotic members of the Bcl-2 family, the lipid composition of the mitochondrial membranes is increasingly recognized to modulate MMP and hence cell death. The unphysiological accumulation of cholesterol in mitochondrial membranes regulates their physical properties, faciliating or impairing MMP during Bax and death ligand-induced cell death depending on the level of mitochondrial GSH (mGSH), which in turn regulates the oxidation status of cardiolipin. Cholesterol-mediated mGSH depletion stimulates TNF-induced reactive oxygen species and subsequent cardiolipin peroxidation, which destabilizes the lipid bilayer and potentiates Bax-induced membrane permeabilization. These data suggest that the balance of mitochondrial cholesterol to peroxidized cardiolipin regulates mitochondrial membrane properties and permeabilization, emerging as a rheostat in cell death.
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影响因子：
64.5
作者：
Du, CY;Fang, M;Wang, XD
通讯作者：
Wang, XD
影响因子：
3
作者：
Colell, Anna;Fernandez, Anna;Fernandez-Checa, Jose C.
通讯作者：
Fernandez-Checa, Jose C.
影响因子：
4.3
作者：
Halestrap, AP;Connern, CP;Kerr, PM
通讯作者：
Kerr, PM
影响因子：
14.8
作者：
Kagan, VE;Tyurin, VA;Borisenko, GG
通讯作者：
Borisenko, GG
DOI：
10.1083/jcb.143.5.1353
发表时间：
1998-11-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kawahara A;Ohsawa Y;Matsumura H;Uchiyama Y;Nagata S
通讯作者：
Nagata S