Modeling Mitochondrial Bioenergetics with Integrated Volume Dynamics
Modeling Mitochondrial Bioenergetics with Integrated Volume Dynamics
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DOI：
10.1371/journal.pcbi.1000632
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Rundell, Ann E.
中科院分区：
文献类型：
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作者：
Bazil, Jason N.;Buzzard, Gregery T.;Rundell, Ann E.
线粒体生物能学的数学模型提供了强大的分析工具，有助于解释实验数据并促进实验设计，以阐明支持的生化和物理过程。作为构建完整的生理上忠实的线粒体生物能学模型的下一步，根据先前的努力，开发了一个针对心脏线粒体生物能的数学模型，并使用瞬态和稳态数据进行了证实。该模型由线粒体生物能学的几个修改速率函数、集成钙动力学以及 K+ 循环及其对线粒体生物能学和基质体积调节的影响的详细描述组成。使用模型模拟将 42 个可调参数拟合到由 32 条数据曲线组成的四个独立实验数据集。在模型开发过程中，必须采用某种网络拓扑，并且明确约束一些关于不确定或未观察到的实验因素和条件的假设，以便忠实地再现所有数据集。对这些认识进行了讨论，它们的必要性有助于促进对线粒体生物能量学的集体理解。
Mathematical models of mitochondrial bioenergetics provide powerful analytical tools to help interpret experimental data and facilitate experimental design for elucidating the supporting biochemical and physical processes. As a next step towards constructing a complete physiologically faithful mitochondrial bioenergetics model, a mathematical model was developed targeting the cardiac mitochondrial bioenergetic based upon previous efforts, and corroborated using both transient and steady state data. The model consists of several modified rate functions of mitochondrial bioenergetics, integrated calcium dynamics and a detailed description of the K+-cycle and its effect on mitochondrial bioenergetics and matrix volume regulation. Model simulations were used to fit 42 adjustable parameters to four independent experimental data sets consisting of 32 data curves. During the model development, a certain network topology had to be in place and some assumptions about uncertain or unobserved experimental factors and conditions were explicitly constrained in order to faithfully reproduce all the data sets. These realizations are discussed, and their necessity helps contribute to the collective understanding of the mitochondrial bioenergetics.