Complex oscillatory redox dynamics with signaling potential at the edge between normal and pathological mitochondrial function.
Complex oscillatory redox dynamics with signaling potential at the edge between normal and pathological mitochondrial function.
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DOI：
10.3389/fphys.2014.00257
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发表时间：
2014
影响因子：
4
通讯作者：
Aon MA
中科院分区：
文献类型：
--
作者：
Kembro JM;Cortassa S;Aon MA
振荡行为赋予功能节律的计时特性代表了生命系统中进化上保守的特征。线粒体网络作为计时器发挥功能，最大化能量输出，同时在与信号传导相容的生理水平内调节活性氧（ROS）。在这项工作中，我们探索了时间保持功能依赖于线粒体动力学的潜力，并验证了两室线粒体能量-氧化还原（ME-R）计算模型，该模型考虑了（a）四个主要的氧化还原对[NADH，NADPH，GSH，Trx（SH）2]，（B）清除系统（谷胱甘肽，硫氧还蛋白，超氧化物歧化酶，过氧化氢酶）分布在基质和基质外的隔室，和（c）运输的活性氧物种之间。在这里，我们描述的ME-R模型可以表现出高度复杂的振荡动力学的能量/氧化还原变量和ROS物种，由至少五个频率调制的振幅和周期，根据功率谱分析。通过稳定性分析，我们描述了稳定状态的程度，对复杂的振荡行为是依赖于丰富的Mn和Cu，Zn SOD，和它们的相互作用与ROS的生产在呼吸链。大的参数区域对应的振荡动力学越来越复杂的波形，在低Cu，Zn SOD浓度作为锰SOD的函数。在较高水平的Cu，Zn SOD的振荡域大大减少。有趣的是，复杂振荡的领域位于正常和病理性线粒体能量行为之间的边缘，其特征在于氧化应激。我们的结论是，复杂的振荡动力学可以代表一个频率和振幅调制的H2 O2信号机制，产生强烈的氧化应激。通过调节SOD，细胞可以在相对恒定性和应激氧化还原/能量条件下所需的灵活性之间进化出一种适应性妥协。
The time-keeping properties bestowed by oscillatory behavior on functional rhythms represent an evolutionarily conserved trait in living systems. Mitochondrial networks function as timekeepers maximizing energetic output while tuning reactive oxygen species (ROS) within physiological levels compatible with signaling. In this work, we explore the potential for timekeeping functions dependent on mitochondrial dynamics with the validated two-compartment mitochondrial energetic-redox (ME-R) computational model, that takes into account (a) four main redox couples [NADH, NADPH, GSH, Trx(SH)2], (b) scavenging systems (glutathione, thioredoxin, SOD, catalase) distributed in matrix and extra-matrix compartments, and (c) transport of ROS species between them. Herein, we describe that the ME-R model can exhibit highly complex oscillatory dynamics in energetic/redox variables and ROS species, consisting of at least five frequencies with modulated amplitudes and period according to power spectral analysis. By stability analysis we describe that the extent of steady state—as against complex oscillatory behavior—was dependent upon the abundance of Mn and Cu, Zn SODs, and their interplay with ROS production in the respiratory chain. Large parametric regions corresponding to oscillatory dynamics of increasingly complex waveforms were obtained at low Cu, Zn SOD concentration as a function of Mn SOD. This oscillatory domain was greatly reduced at higher levels of Cu, Zn SOD. Interestingly, the realm of complex oscillations was located at the edge between normal and pathological mitochondrial energetic behavior, and was characterized by oxidative stress. We conclude that complex oscillatory dynamics could represent a frequency- and amplitude-modulated H2O2 signaling mechanism that arises under intense oxidative stress. By modulating SOD, cells could have evolved an adaptive compromise between relative constancy and the flexibility required under stressful redox/energetic conditions.
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DOI：
10.1073/pnas.0307156101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Aon, MA;Cortassa, S;O'Rourke, B
通讯作者：
O'Rourke, B
影响因子：
3.4
作者：
Cortassa, S;Aon, MA;O'Rourke, B
通讯作者：
O'Rourke, B
DOI：
10.1111/j.1463-1326.2010.01266.x
发表时间：
2010-10
期刊：
Diabetes, obesity & metabolism
影响因子：
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作者：
Jones DP;Go YM
通讯作者：
Go YM
影响因子：
4.8
作者：
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通讯作者：
Brookes, Paul S.
影响因子：
3.7
作者：
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