Catalytic Coupling of Oxidative Phosphorylation, ATP Demand, and Reactive Oxygen Species Generation
Catalytic Coupling of Oxidative Phosphorylation, ATP Demand, and Reactive Oxygen Species Generation
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DOI：
10.1016/j.bpj.2015.09.036
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发表时间：
2016-02-23
影响因子：
3.4
通讯作者：
Vinnakota, Kalyan C.
中科院分区：
文献类型：
--
作者：
Bazil, Jason N.;Beard, Daniel A.;Vinnakota, Kalyan C.
心脏线粒体能量代谢的相互竞争的模型是高度争议的。此外，活性氧（ROS）的产生和清除机制尚不清楚。为了加深我们对这些过程的理解，我们开发了一个计算机模型来整合氧化磷酸化和ROS生成的生物物理过程。该模型采用生理条件和负荷下大鼠离体心脏线粒体的实验数据进行校准。模型模拟表明，醌池氧化还原态的变化是导致配合物III明显的无机磷酸盐活化的原因。模型模拟预测，在生理工作条件下，复合物III比复合物i产生更多的ROS。然而，在病理条件下，这种关系被逆转。最后，模型分析揭示了由琥珀酸水平升高引起的高度减少的醌池可能是缺血后再灌注期间ROS爆发的原因。
Competing models of mitochondrial energy metabolism in the heart are highly disputed. In addition, the mechanisms of reactive oxygen species (ROS) production and scavenging are not well understood. To deepen our understanding of these processes, a computer model was developed to integrate the biophysical processes of oxidative phosphorylation and ROS generation. The model was calibrated with experimental data obtained from isolated rat heart mitochondria subjected to physiological conditions and workloads. Model simulations show that changes in the quinone pool redox state are responsible for the apparent inorganic phosphate activation of complex III. Model simulations predict that complex III is responsible for more ROS production during physiological working conditions relative to complex I. However, this relationship is reversed under pathological conditions. Finally, model analysis reveals how a highly reduced quinone pool caused by elevated levels of succinate is likely responsible for the burst of ROS seen during reperfusion after ischemia.