Matching ATP supply and demand in mammalian heart: in vivo, in vitro, and in silico perspectives.

Matching ATP supply and demand in mammalian heart: in vivo, in vitro, and in silico perspectives.
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DOI:
10.1111/j.1749-6632.2009.05093.x
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发表时间:
2010-02
影响因子:
5.2
通讯作者:
Sollott SJ
Sollott SJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yaniv Y;Juhaszova M;Nuss HB;Wang S;Zorov DB;Lakatta EG;Sollott SJ

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虽然心脏迅速调整心输出量以匹配身体的循环需求,但确保有足够的ATP可用来执行所需的心脏功的调节机制尚不完全清楚。有两种机制被认为是关键的调节机制:(1)ADP和PI浓度--胞浆中的ATP利用/水解增加了ADP和PI向线粒体的通量,从而增加了可用于产生ATP的底物的数量;(2)钙浓度--ATP的利用/水解与胞质游离钙和线粒体钙的变化相耦合,后者控制参与ATP产生的线粒体酶对钙的依赖的激活。在这里,我们在现有的实验和理论证据的基础上,讨论了每种可能的调控机制和精确的分子靶标(脱氢酶,ATP合成酶)的发展前景。数据合成可以产生新的假设和实验设计,以解决心脏中正在进行的能源供需匹配之谜。
Although the heart rapidly adapts cardiac output to match the body’s circulatory demands, the regulatory mechanisms ensuring that sufficient ATP is available to perform the required cardiac work are not completely understood. Two mechanisms have been suggested to serve as key regulators: (1) ADP and Pi concentrations—ATP utilization/hydrolysis in the cytosol increases ADP and Pi fluxes to mitochondria and hence the amount of available substrates for ATP production increases; and (2) Ca2+ concentration—ATP utilization/hydrolysis is coupled to changes in free cytosolic calcium and mitochondrial calcium, the latter controlling Ca2+-dependent activation of mitochondrial enzymes taking part in ATP production. Here we discuss the evolving perspectives of each of the putative regulatory mechanisms and the precisemolecular targets (dehydrogenase enzymes, ATP synthase) based on existing experimental and theoretical evidence. The data synthesis can generate novel hypotheses and experimental designs to solve the ongoing enigma of energy supply–demand matching in the heart.
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