半胱氨酸蛋白酶
细胞色素c
线粒体
生物
效应器
细胞生物学
细胞凋亡
凋亡体
去极化
线粒体凋亡诱导通道
活性氧
半胱氨酸蛋白酶-9
程序性细胞死亡
内源性凋亡
生物化学
生物物理学
作者
Enriqué Cepero,Anne M. King,Lane M Coffey,Rebeka G Perez,Lawrence H. Boise
出处
期刊:Oncogene
[Springer Nature]
日期:2005-06-20
卷期号:24 (42): 6354-6366
被引量:43
标识
DOI:10.1038/sj.onc.1208793
摘要
Proapoptotic Bcl-2 family members alter mitochondrial permeability resulting in the release of apoptogenic factors that initiate a caspase cascade. These changes are well described; however, the effects of caspases on mitochondrial function are less well characterized. Here we describe the consequence of caspase-9 and effector caspase inhibition on mitochondrial physiology during intrinsic cell death. Caspase inhibition prevents the complete loss of mitochondrial membrane potential without affecting cytochrome c release. When effector caspases are inhibited, mitochondria become uncoupled and produce reactive oxygen species. Interestingly, the effector caspase-mediated depolarization of the mitochondria occurs independent of the activity of complexes I–IV of the electron transport chain. In contrast, caspase-9 inhibition prevents mitochondrial uncoupling and ROS production and allows for continued electron transport despite the release of cytochrome c. Taken together, these data suggest that activated caspase-9 prevents the accessibility of cytochrome c to complex III, resulting in the production of reactive oxygen species, and that effector caspases may depolarize mitochondria to terminate ROS production and preserve an apoptotic phenotype.
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