The Scale-Free Dynamics of Eukaryotic Cells
The Scale-Free Dynamics of Eukaryotic Cells
复制标题
DOI：
10.1371/journal.pone.0003624
复制
发表时间：
2008-11-04
期刊：
影响因子：
3.7
通讯作者：
Lloyd, David
中科院分区：
文献类型：
--
作者：
Aon, Miguel A.;Roussel, Marc R.;Lloyd, David
生物过程的时间组织需要在同步时基上进行大规模并行处理。我们利用相对色散 (RDA) 和功率谱 (PSA) 分析，分析了从酿酒酵母和分离的心肌细胞的生物能振荡输出获得的时间序列数据。这些分析揭示了观察到的动态中广泛的频率分布和长期记忆的证据。此外，RDA 和 PSA 表明，两个系统中的生物能动力学表现出至少 3 个数量级的分形缩放，并且这种缩放遵循逆幂律。因此，我们得出结论，在酿酒酵母和心肌细胞中，体内动力学是无标度的。将 RDA 和 PSA 应用于线粒体功能计算机模型生成的数据表明，在酵母和心肌细胞中，调节无标度行为的潜在机制是相似的。我们使用单细胞在体内验证了这一发现，并用 4-氯地西泮减弱了线粒体内膜阴离子通道的活性，以表明 NAD(P)H 和活性氧 (ROS) 的振荡可以在这两个进化上距离较远的物种中减弱。综上所述，这些数据有力地支持了我们的假设，即由细胞质和线粒体过程驱动的与氧化还原循环耦合的 ROS 的产生是观察到的节律性和无标度动力学的核心。我们认为，无标度生物能量动力学的运行在整合细胞功能方面发挥着基础作用，同时为对环境的稳健而灵活的响应提供了框架。
Temporal organization of biological processes requires massively parallel processing on a synchronized time-base. We analyzed time-series data obtained from the bioenergetic oscillatory outputs of Saccharomyces cerevisiae and isolated cardiomyocytes utilizing Relative Dispersional (RDA) and Power Spectral (PSA) analyses. These analyses revealed broad frequency distributions and evidence for long-term memory in the observed dynamics. Moreover RDA and PSA showed that the bioenergetic dynamics in both systems show fractal scaling over at least 3 orders of magnitude, and that this scaling obeys an inverse power law. Therefore we conclude that in S. cerevisiae and cardiomyocytes the dynamics are scale-free in vivo. Applying RDA and PSA to data generated from an in silico model of mitochondrial function indicated that in yeast and cardiomyocytes the underlying mechanisms regulating the scale-free behavior are similar. We validated this finding in vivo using single cells, and attenuating the activity of the mitochondrial inner membrane anion channel with 4-chlorodiazepam to show that the oscillation of NAD(P)H and reactive oxygen species (ROS) can be abated in these two evolutionarily distant species. Taken together these data strongly support our hypothesis that the generation of ROS, coupled to redox cycling, driven by cytoplasmic and mitochondrial processes, are at the core of the observed rhythmicity and scale-free dynamics. We argue that the operation of scale-free bioenergetic dynamics plays a fundamental role to integrate cellular function, while providing a framework for robust, yet flexible, responses to the environment.