Griffiths Elinor J, Balaska Dirki, Cheng Wendy H Y
Department of Biochemistry and Bristol Heart Institute, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):856-64. doi: 10.1016/j.bbabio.2010.02.022. Epub 2010 Feb 24.
Regulation of intramitochondrial free calcium ([Ca2+]m) is critical in both physiological and pathological functioning of the heart. The full extent and importance of the role of [Ca2+]m is becoming apparent as evidenced by the increasing interest and work in this area over the last two decades. However, controversies remain, such as the existence of beat-to-beat mitochondrial Ca2+ transients; the role of [Ca2+]m in modulating whole-cell Ca2+ signalling; whether or not an increase in [Ca2+]m is essential to couple ATP supply and demand; and the role of [Ca2+]m in cell death by both necrosis and apoptosis, especially in formation of the mitochondrial permeability transition pore. The role of [Ca2+]m in heart failure is an area that has also recently been highlighted. [Ca2+]m can now be measured reasonably specifically in intact cells and hearts thanks to developments in fluorescent indicators and targeted proteins and more sensitive imaging technology. This has revealed interactions of the mitochondrial Ca2+ transporters with those of the sarcolemma and sarcoplasmic reticulum, and has gone a long way to bringing the mitochondrial Ca2+ transporters to the forefront of cardiac research. Mitochondrial Ca2+ uptake occurs via the ruthenium red sensitive Ca2+ uniporter (mCU), and efflux via an Na+/Ca2+ exchanger (mNCX). The purification and cloning of the transporters, and development of more specific inhibitors, would produce a step-change in our understanding of the role of these apparently critical but still elusive proteins. In this article we will summarise the key physiological roles of [Ca2+]m in ATP production and cell Ca2+ signalling in both adult and neonatal hearts, as well as highlighting some of the controversies in these areas. We will also briefly discuss recent ideas on the interactions of nitric oxide with [Ca2+]m.
线粒体内游离钙（[Ca2+]m）的调节对心脏的生理和病理功能都至关重要。过去二十年来，该领域的研究兴趣和工作不断增加，这表明[Ca2+]m作用的全部范围和重要性正日益显现。然而，争议仍然存在，例如逐搏线粒体钙瞬变的存在；[Ca2+]m在调节全细胞钙信号中的作用；[Ca2+]m的增加对于匹配ATP供应与需求是否至关重要；以及[Ca2+]m在坏死和凋亡导致的细胞死亡中的作用，尤其是在线粒体通透性转换孔的形成中。[Ca2+]m在心力衰竭中的作用也是最近受到关注的一个领域。由于荧光指示剂、靶向蛋白和更灵敏成像技术的发展，现在可以在完整细胞和心脏中较为特异性地测量[Ca2+]m。这揭示了线粒体钙转运体与肌膜和肌浆网钙转运体之间的相互作用，在很大程度上将线粒体钙转运体推到了心脏研究的前沿。线粒体钙摄取通过钌红敏感的钙单向转运体（mCU）进行，而外流则通过钠/钙交换体（mNCX）。这些转运体的纯化、克隆以及更特异性抑制剂的开发，将使我们对这些看似关键但仍难以捉摸的蛋白质的作用的理解发生飞跃。在本文中，我们将总结[Ca2+]m在成年和新生心脏ATP生成和细胞钙信号中的关键生理作用，并突出这些领域中的一些争议。我们还将简要讨论一氧化氮与[Ca2+]m相互作用的最新观点。
