Gene Center, Department of Biochemistry, Ludwig-Maximilians Universität München, Munich, 81377, Germany.
Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC), Helmholtz Zentrum München and German National Diabetes Center (DZD), Neuherberg, 85764, Germany.
J Physiol. 2018 Jul;596(14):2717-2733. doi: 10.1113/JP274959. Epub 2018 Feb 18.
Mitochondria are pivotal organelles in calcium (Ca ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca homeostasis.
线粒体在钙（Ca）处理和信号转导中起着关键作用，是许多对细胞生命至关重要的过程的细胞内检查点。线粒体 Ca 稳态的改变与多种病理状况有关，并且在几种人类疾病的发病机制中至关重要。人们已经努力利用线粒体 Ca 转运机制进行治疗干预，但是目前缺乏能够直接且有选择性地调节线粒体 Ca 稳态的药理学化合物。然而，随着对涉及线粒体 Ca 内流和外流途径的主要参与者的遗传鉴定的突破性发现，以及对这些分子系统功能的深入了解的最新提示，出现了新的途径。在这里，我们回顾了对线粒体 Ca 稳态的机制和调节及其对生理学和人类疾病的贡献的理解的最新进展。我们还介绍并评论了针对线粒体 Ca 稳态的系统水平药理学靶向的最新进展。
