Mitochondrial calcium and the regulation of metabolism in the heart.
Mitochondrial calcium and the regulation of metabolism in the heart.
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DOI：
10.1016/j.yjmcc.2014.10.019
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发表时间：
2015-01
影响因子：
5
通讯作者：
Lederer WJ
中科院分区：
文献类型：
--
作者：
Williams GS;Boyman L;Lederer WJ
心脏对三磷酸腺苷(ATP)的消耗会随着能量需求的增加而发生巨大的变化，从休息到剧烈活动。线粒体ATP的产生是这种代谢反应的中心，因为心脏在很大程度上依赖于氧化磷酸化作为其细胞内ATP的来源。已有的重要证据表明，钙离子在线粒体产生三磷酸腺苷的过程中起着关键作用。本文对线粒体基质中的钙离子浓度([Ca~(2+)]m)在调节线粒体产生ATP中起关键作用的证据进行了综述，并重点介绍了目前正在积极研究的这一过程的一些方面。重要的是，当前关于跨内线粒体膜(IMM)的钙离子双向移动的定量信息被分成两个部分来检验。首先，我们回顾了钙离子如何内流到线粒体基质中依赖于线粒体钙离子通道(即线粒体钙单转运体或MCU)。其中包括微通道开放概率(PO)与细胞内钙离子浓度([Ca~(2+)]i)和线粒体膜电位(ΔΨ_m)的关系。其次，我们讨论了基于MCU的钙离子内流和基于线粒体Na+/Ca~(2+)交换器(NCLX)的钙流出之间的动态平衡是如何决定稳态的[钙]_m的。这些稳定的[Ca2+]m水平被认为是由于对三羧酸循环(TCA)的线粒体酶(TCA)、电子传递链(ETC)的蛋白质以及F1F0 ATP合成酶本身的钙依赖调节而调节代谢能量供应。最后，我们讨论了在病理条件下，[Ca~(2+)]m在影响线粒体反应中所起的作用。
Consumption of adenosine triphosphate (ATP) by the heart can change dramatically as the energetic demands increase from a period of rest to strenuous activity. Mitochondrial ATP production is central to this metabolic response since the heart relies largely on oxidative phosphorylation as its source of intracellular ATP. Significant evidence has been acquired indicating that Ca2+ plays a critical role in regulating ATP production by the mitochondria. Here the evidence that the Ca2+ concentration in the mitochondrial matrix ([Ca2+]m) plays a pivotal role in regulating ATP production by the mitochondria is critically reviewed and aspects of this process that are under current active investigation are highlighted. Importantly, current quantitative information on the bidirectional Ca2+ movement across the inner mitochondrial membrane (IMM) is examined in two parts. First, we review how Ca2+ influx into the mitochondrial matrix depends on the mitochondrial Ca2+ channel (i.e., the mitochondrial calcium uniporter or MCU). This discussion includes how the MCU open probability (PO) depends on the cytosolic Ca2+ concentration ([Ca2+]i) and on the mitochondrial membrane potential (ΔΨm). Second, we discuss how steady-state [Ca2+]m is determined by the dynamic balance between this MCU-based Ca2+ influx and mitochondrial Na+/Ca2+ exchanger (NCLX) based Ca2+ efflux. These steady-state [Ca2+]m levels are suggested to regulate the metabolic energy supply due to Ca2+-dependent regulation of mitochondrial enzymes of the tricarboxylic acid cycle (TCA), the proteins of the electron transport chain (ETC), and the F1F0 ATP synthase itself. We conclude by discussing the roles played by [Ca2+]m in influencing mitochondrial responses under pathological conditions.
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影响因子：
4.3
作者：
Bonora, Massimo;Bononi, Angela;Pinton, Paolo
通讯作者：
Pinton, Paolo
DOI：
10.1111/j.1460-9568.2010.07576.x
发表时间：
2011-03
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Barsukova A;Komarov A;Hajnóczky G;Bernardi P;Bourdette D;Forte M
通讯作者：
Forte M
影响因子：
3
作者：
Bazil, Jason N.;Blomeyer, Christoph A.;Pradhan, Ranjan K.;Camara, Amadou K. S.;Dash, Ranjan K.
通讯作者：
Dash, Ranjan K.
影响因子：
5
作者：
Baines, Christopher P.
通讯作者：
Baines, Christopher P.
影响因子：
2.9
作者：
Blinova, Ksenia;Levine, Rodney L.;Boja, Emily S.;Griffiths, Gary L.;Shi, Zhen-Dan;Ruddy, Brian;Balaban, Robert S.
通讯作者：
Balaban, Robert S.