Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process.

Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process.
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细胞色素 c 在细胞凋亡过程中线粒体外膜透化后维持线粒体跨膜电位和 ATP 生成。

DOI:
10.1083/jcb.153.2.319
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发表时间:
2001-04-16
影响因子:
7.8
通讯作者:
Green, DR
Green, DR
中科院分区:
生物学1区
文献类型:
--
作者:
Waterhouse, NJ;Goldstein, JC;von Ahsen, O;Schuler, M;Newmeyer, DD;Green, DR

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在细胞凋亡过程中,随着线粒体外膜变得可渗透,细胞色素 c 被释放到胞质溶胶中,这会触发 caspase 激活。这种释放对线粒体代谢的影响尚不清楚。通过单细胞分析,我们发现当 caspase 活性受到抑制时,线粒体外膜透化会导致线粒体跨膜电位快速去极化,在接下来的 30-60 分钟内恢复到原始水平,然后维持下去。外膜透化后,线粒体可以利用细胞质细胞色素 c 来维持线粒体跨膜电位和 ATP 产生。此外,细胞色素 c 的释放和细胞凋亡在线粒体解偶联的细胞中正常进行。这些研究表明,细胞色素c的释放不会影响线粒体内膜的完整性,并且在没有caspase激活的情况下,细胞色素c释放后可以维持线粒体功能。
During apoptosis, cytochrome c is released into the cytosol as the outer membrane of mitochondria becomes permeable, and this acts to trigger caspase activation. The consequences of this release for mitochondrial metabolism are unclear. Using single-cell analysis, we found that when caspase activity is inhibited, mitochondrial outer membrane permeabilization causes a rapid depolarization of mitochondrial transmembrane potential, which recovers to original levels over the next 30–60 min and is then maintained. After outer membrane permeabilization, mitochondria can use cytoplasmic cytochrome c to maintain mitochondrial transmembrane potential and ATP production. Furthermore, both cytochrome c release and apoptosis proceed normally in cells in which mitochondria have been uncoupled. These studies demonstrate that cytochrome c release does not affect the integrity of the mitochondrial inner membrane and that, in the absence of caspase activation, mitochondrial functions can be maintained after the release of cytochrome c.
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