Coordinated behavior of mitochondria in both space and time: A reactive oxygen species-activated wave of mitochondrial depolarization

Coordinated behavior of mitochondria in both space and time: A reactive oxygen species-activated wave of mitochondrial depolarization
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DOI:
10.1529/biophysj.103.035097
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发表时间:
2004-09-01
影响因子:
3.4
通讯作者:
Westerhoff, HV
Westerhoff, HV
中科院分区:
生物学3区
文献类型:
--
作者:
Brady, NR;Elmore, SP;Westerhoff, HV

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活性氧(ROS)可以通过激活线粒体通透性过渡孔(MPTP)触发线粒体ROS生成的短暂爆发,这种现象被称为ROS诱导的ROS释放(RIRR)。本研究的目的是研究心肌细胞离散区域ROS的产生是否有助于在整个细胞中传播rirr介导的线粒体去极化。我们的实验表明,局部的RIRR激活了RIRR介导的线粒体膜电位波动(时间周期:3-10分钟)或细胞线粒体去极化的行波(速度:类似于5妈妈/分钟)。这两种现象似乎都是由线粒体通透性过渡孔介导的,并最终包括离体大鼠和兔心肌细胞的大部分线粒体群。此外,去极化往往是可逆的;去极化波之后是线粒体的快速复极化波(类似于40妈妈/分钟)。我们发现,在分离的成人心肌细胞中,RIRR可以发挥沟通线粒体通透性从一个线粒体到另一个线粒体的作用。
Reactive oxygen species (ROS) can trigger a transient burst of mitochondrial ROS production via ROS activation of the mitochondrial permeability transition pore (MPTP), a phenomenon termed ROS-induced ROS release (RIRR). The goal of this study was to investigate if the generation of ROS in a discrete region of a cardiomyocyte could serve to propagate RIRR-mediated mitochondrial depolarizations throughout a cell. Our experiments revealed that localized RIRR activated either RIRR-mediated fluctuations in mitochondrial membrane potential (time period: 3-10 min) or a traveling wave of depolarization of the cell's mitochondria (velocity: similar to5 mum/min). Both phenomena appeared to be mediated by the mitochondrial permeability transition pore and eventually encompassed the majority of the mitochondrial population of both isolated rat and rabbit cardiomyocytes. Furthermore, depolarization was often reversible; the waves of depolarization were then followed by a rapid (similar to40 mum/min) repolarization wave of the mitochondria. We show that the RIRR can function to communicate the mitochondrial permeability transition from one mitochondrion to another in the isolated adult cardiomyocyte.