Cardiovascular Research Center, Rhode Island Hospital, Providence, RI, USA; Department of Medicine, Division of Cardiology, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Cardiovascular Research Center, Rhode Island Hospital, Providence, RI, USA; Department of Medicine, Division of Cardiology, The Warren Alpert Medical School of Brown University, Providence, RI, USA; Lillehei Heart Institute, Department of Medicine, Cardiovascular Division, University of Minnesota, Minneapolis, MN, USA.
Arch Biochem Biophys. 2019 Mar 15;663:276-287. doi: 10.1016/j.abb.2019.01.027. Epub 2019 Jan 23.
Recent discoveries of the molecular identity of mitochondrial Ca influx/efflux mechanisms have placed mitochondrial Ca transport at center stage in views of cellular regulation in various cell-types/tissues. Indeed, mitochondria in cardiac muscles also possess the molecular components for efficient uptake and extraction of Ca. Over the last several years, multiple groups have taken advantage of newly available molecular information about these proteins and applied genetic tools to delineate the precise mechanisms for mitochondrial Ca handling in cardiomyocytes and its contribution to excitation-contraction/metabolism coupling in the heart. Though mitochondrial Ca has been proposed as one of the most crucial secondary messengers in controlling a cardiomyocyte's life and death, the detailed mechanisms of how mitochondrial Ca regulates physiological mitochondrial and cellular functions in cardiac muscles, and how disorders of this mechanism lead to cardiac diseases remain unclear. In this review, we summarize the current controversies and discrepancies regarding cardiac mitochondrial Ca signaling that remain in the field to provide a platform for future discussions and experiments to help close this gap.
近年来，人们对线粒体 Ca 流入/流出机制的分子特性有了新的认识，这使得线粒体 Ca 转运在各种细胞/组织的细胞调节方面处于中心地位。事实上，心肌细胞中的线粒体也拥有有效摄取和提取 Ca 的分子成分。在过去的几年中，多个研究小组利用这些蛋白质的新的分子信息，并应用遗传工具，来阐明心肌细胞中线粒体 Ca 处理的精确机制及其对心脏兴奋-收缩/代谢偶联的贡献。虽然线粒体 Ca 已被提出作为控制心肌细胞生死的最重要的第二信使之一，但线粒体 Ca 如何调节心肌中线粒体和细胞的生理功能的详细机制，以及这种机制的紊乱如何导致心脏病，仍然不清楚。在这篇综述中，我们总结了该领域中关于心脏线粒体 Ca 信号的现存争议和差异，为未来的讨论和实验提供了一个平台，以帮助缩小这一差距。
