Cardiolipin deficiency releases cytochrome c from the inner mitochondrial membrane and accelerates stimuli-elicited apoptosis
Cardiolipin deficiency releases cytochrome c from the inner mitochondrial membrane and accelerates stimuli-elicited apoptosis
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DOI：
10.1038/sj.cdd.4402020
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发表时间：
2007-03-01
影响因子：
12.4
通讯作者：
Frohman, M. A.
中科院分区：
文献类型：
--
作者：
Choi, S-Y;Gonzalvez, F.;Frohman, M. A.
心磷脂（CL）是由心磷脂合成酶（CLS）合成的一种心磷脂。我们在这里描述了一个CLS的人类基因和它的分析通过RNAi敲低细胞凋亡的进展。虽然线粒体膜电位是不变的细胞只含有25%的正常量的CL，游离细胞色素c（cyt。c）在膜间隙中检测到，并且线粒体表现出重组嵴的迹象。然而，细胞色素的释放。线粒体中的C仍然需要凋亡刺激。在CL缺陷细胞中观察到对凋亡信号的敏感性增加和凋亡速率加快，随后继发性坏死水平升高。细胞凋亡被认为是通过截短的Bid（tBid）与线粒体CL结合，然后CL氧化，导致细胞色素。C释放在CL缺陷细胞中观察到的夸大和加速的细胞凋亡与膜电位的加速降低和细胞周期的增加相匹配。c释放，但不是通过降低tBid结合。提示CL/cyt. c关系在凋亡进展中是重要的，并且调节CL氧化或/和脱酰化可能代表可能的治疗靶点。
Cardiolipin (CL) is a mitochondria-specific phospholipid synthesized by CL synthase (CLS). We describe here a human gene for CLS and its analysis via RNAi knockdown on apoptotic progression. Although mitochondrial membrane potential is unchanged in cells containing only 25% of the normal amount of CL, free cytochrome c (cyt. c) is detected in the intermembrane space and the mitochondria exhibit signs of reorganized cristae. However, the release of cyt. c from the mitochondria still requires apoptotic stimulation. Increased sensitivity to apoptotic signals and accelerated rates of apoptosis are observed in CL-deficient cells, followed by elevated levels of secondary necrosis. Apoptosis is thought to progress via binding of truncated Bid (tBid) to mitochondrial CL, followed by CL oxidation which results in cyt. c release. The exaggerated and accelerated apoptosis observed in CL-deficient cells is matched by an accelerated reduction in membrane potential and increased cyt. c release, but not by decreased tBid binding. This study suggests that the CL/cyt. c relationship is important in apoptotic progression and that regulating CL oxidation or/and deacylation could represent a possible therapeutic target.