Comparative kinetic analysis reveals that inducer-specific ion release precedes the mitochondrial permeability transition

Comparative kinetic analysis reveals that inducer-specific ion release precedes the mitochondrial permeability transition
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DOI:
10.1016/j.bbabio.2005.05.009
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发表时间:
2005-07-15
影响因子:
4.3
通讯作者:
Brown, AM
Brown, AM
中科院分区:
生物学2区
文献类型:
--
作者:
Krasnikov, BF;Zorov, DB;Brown, AM

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在线粒体膜通透性转变(MPT)之前的多个事件之间的关系尚不清楚。描述了新开发的仪器和计算方法的结合。仪器创新是一种高分辨率的数字仪器,用于同时实时测量四种线粒体参数,作为呼吸速率、膜电位、钙离子运输和线粒体肿胀的指标。介绍了一种计算方法,跟踪线粒体的部分已经经历了孔打开。这种方法允许在单一时间尺度上进行多次比较。计算方法对研究复杂线粒体现象的有效性进行了评估,线粒体经历由Ca2+,苯larsin氧化物或alamethicin诱导的MPT。选择性离子泄漏被观察到在渗透性转变之前,这是诱导剂特有的。这些结果说明了与诱导渗透率转变相关的诱导剂特异性序列变化的发生。分析分离的线粒体的多个线粒体参数之间的时间关系应该提供深入了解这些反应的机制。(c) 2005 Elsevier B.V.版权所有
Relationships among the multiple events that precede the mitochondrial membrane permeability transition (MPT) are not yet clearly understood. A combination of newly developed instrumental and computational approaches to this problem is described. The instrumental innovation is a high-resolution digital apparatus for the simultaneous, real-time measurement of four mitochondrial parameters as indicators of the respiration rate, membrane potential, calcium ion transport, and mitochondrial swelling. A computational approach is introduced that tracks the fraction of mitochondria that has undergone pore opening. This approach allows multiple comparisons on a single time scale. The validity of the computational approach for studying complex mitochondrial phenomena was evaluated with mitochondria undergoing an MPT induced by Ca2+, phenylarsine oxide or alamethicin. Selective ion leaks were observed that precede the permeability transition and that are inducer specific. These results illustrate the occurrence of inducer-specific sequential changes associated with the induction of the permeability transition. Analysis of the temporal relationship among the multiple mitochondrial parameters of isolated mitochondria should provide insights into the mechanisms underlying these responses. (c) 2005 Elsevier B.V. All rights reserved.