Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis.
Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis.
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DOI：
10.1083/jcb.200208089
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发表时间：
2003-01-06
期刊：
影响因子：
--
通讯作者：
Green DR
中科院分区：
文献类型：
--
作者：
Ricci JE;Gottlieb RA;Green DR
在细胞凋亡期间，线粒体外膜的透化允许细胞色素c的释放，其诱导半胱天冬酶活化以协调细胞的死亡。线粒体迅速失去其跨膜电位（Δ Km）并产生活性氧（ROS），这两者都可能有助于细胞的解体。在这里，我们表明，无论是快速损失的Δ λ m和ROS的产生是由于激活的半胱天冬酶对线粒体电子传递复合物I和II的影响。半胱天冬酶-3破坏由复合物I和II底物诱导的氧消耗，但不破坏由电子转移到复合物IV诱导的氧消耗。类似地，在复合物I或II底物存在下产生的Δ λ m被半胱天冬酶-3破坏，并产生ROS。通过细胞色素c还原测量的复合物III活性在半胱天冬酶-3处理后保持完整。在凋亡细胞中，依赖于复合物I或II的电子传递和氧消耗以半胱天冬酶依赖的方式被破坏。我们的研究结果表明，细胞色素c释放后，半胱天冬酶的激活反馈到透化的线粒体上，损害线粒体功能（Δ △ m的损失），并通过半胱天冬酶对电子传递链中的复合物I和II的作用产生ROS。
During apoptosis, the permeabilization of the mitochondrial outer membrane allows the release of cytochrome c, which induces caspase activation to orchestrate the death of the cell. Mitochondria rapidly lose their transmembrane potential (ΔΨm) and generate reactive oxygen species (ROS), both of which are likely to contribute to the dismantling of the cell. Here we show that both the rapid loss of ΔΨm and the generation of ROS are due to the effects of activated caspases on mitochondrial electron transport complexes I and II. Caspase-3 disrupts oxygen consumption induced by complex I and II substrates but not that induced by electron transfer to complex IV. Similarly, ΔΨm generated in the presence of complex I or II substrates is disrupted by caspase-3, and ROS are produced. Complex III activity measured by cytochrome c reduction remains intact after caspase-3 treatment. In apoptotic cells, electron transport and oxygen consumption that depends on complex I or II was disrupted in a caspase-dependent manner. Our results indicate that after cytochrome c release the activation of caspases feeds back on the permeabilized mitochondria to damage mitochondrial function (loss of ΔΨm) and generate ROS through effects of caspases on complex I and II in the electron transport chain.
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影响因子：
64.5
作者：
Du, CY;Fang, M;Wang, XD
通讯作者：
Wang, XD
DOI：
10.1083/jcb.200104008
发表时间：
2001-09-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mannick JB;Schonhoff C;Papeta N;Ghafourifar P;Szibor M;Fang K;Gaston B
通讯作者：
Gaston B
影响因子：
4.8
作者：
Bossy-Wetzel, E;Green, DR
通讯作者：
Green, DR
影响因子：
3.4
作者：
FARKAS, DL;WEI, MD;LOEW, LM
通讯作者：
LOEW, LM
DOI：
10.1083/jcb.136.1.215
发表时间：
1997-01-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy NJ;Whyte MK;Gilbert CS;Evan GI
通讯作者：
Evan GI