Modeling the calcium sequestration system in isolated guinea pig cardiac mitochondria.
Modeling the calcium sequestration system in isolated guinea pig cardiac mitochondria.
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DOI：
10.1007/s10863-012-9488-2
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发表时间：
2013-06
影响因子：
3
通讯作者：
Dash, Ranjan K.
中科院分区：
文献类型：
--
作者：
Bazil, Jason N.;Blomeyer, Christoph A.;Pradhan, Ranjan K.;Camara, Amadou K. S.;Dash, Ranjan K.
在高Ca 2+负荷条件下，线粒体外和线粒体隔室中的Ca 2+浓度不显示相互动力学。这是由于线粒体Ca 2+缓冲能力随着Ca 2+负荷的增加而矛盾地增加。在这里，我们开发和表征的线粒体Ca 2+螯合系统的机制，使用离体豚鼠心肌线粒体的实验数据集。所提出的机制阐明了这种现象和其他人在一个数学框架，并集成到一个先前证实的模型氧化磷酸化，包括Na+/Ca 2+循环。集成模型再现了在两个隔室中观察到的钙离子动力学的分离线粒体呼吸丙酮酸后，由钌红和一个弹丸的NaCl的氯化钙。该模型揭示了为什么在Ca 2+外排启动后，相对于相应的线粒体外Ca 2+浓度变化，负载Ca 2+的线粒体的线粒体Ca 2+浓度变化出现显着减轻。通过模拟设定点现象验证了综合模型的正确性。计算结果支持的结论是，钙螯合系统是由至少两个类的钙缓冲。第一类代表典型的Ca 2+缓冲，第二类包括与无定形磷酸钙形成相关的复合物结合事件。随着线粒体中Ca 2+螯合系统的更精确定义，计算机模拟可以帮助开发创新疗法，旨在解决由于线粒体Ca 2+过载而引起的无数并发症。
Under high Ca2+ load conditions, Ca2+ concentrations in the extra-mitochondrial and mitochondrial compartments do not display reciprocal dynamics. This is due to a paradoxical increase in the mitochondrial Ca2+ buffering power as the Ca2+ load increases. Here we develop and characterize a mechanism of the mitochondrial Ca2+ sequestration system using an experimental data set from isolated guinea pig cardiac mitochondria. The proposed mechanism elucidates this phenomenon and others in a mathematical framework and is integrated into a previously corroborated model of oxidative phosphorylation including the Na+/Ca2+ cycle. The integrated model reproduces the Ca2+ dynamics observed in both compartments of the isolated mitochondria respiring on pyruvate after a bolus of CaCl2 followed by ruthenium red and a bolus of NaCl. The model reveals why changes in mitochondrial Ca2+ concentration of Ca2+ loaded mitochondria appear significantly mitigated relative to the corresponding extra-mitochondrial Ca2+ concentration changes after Ca2+ efflux is initiated. The integrated model was corroborated by simulating the set-point phenomenon. The computational results support the conclusion that the Ca2+ sequestration system is composed of at least two classes of Ca2+ buffers. The first class represents prototypical Ca2+ buffering, and the second class encompasses the complex binding events associated with the formation of amorphous calcium phosphate. With the Ca2+ sequestration system in mitochondria more precisely defined, computer simulations can aid in the development of innovative therapeutics aimed at addressing the myriad of complications that arise due to mitochondrial Ca2+ overload.
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影响因子：
4.8
作者：
Chalmers, S;Nicholls, DG
通讯作者：
Nicholls, DG
DOI：
10.1073/pnas.47.11.1744
发表时间：
1961-01-01
影响因子：
11.1
作者：
DELUCA, HF;ENGSTROM, GW
通讯作者：
ENGSTROM, GW
影响因子：
4.3
作者：
Bazil, Jason N.;Buzzard, Gregery T.;Rundell, Ann E.
通讯作者：
Rundell, Ann E.
DOI：
10.1016/0005-2736(88)90509-3
发表时间：
1988-10-20
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
KAPUS, A;LUKACS, GL;FONYO, A
通讯作者：
FONYO, A
影响因子：
5.5
作者：
Dash, Ranjan K.;Beard, Daniel A.
通讯作者：
Beard, Daniel A.