Department of Medicine, Duke University School of Medicine, Durham, NC 27705, United States.
Cell Calcium. 2022 Jun;104:102586. doi: 10.1016/j.ceca.2022.102586. Epub 2022 Mar 28.
Despite a growing number of successful therapies, heart failure remains the most common cause of death and disability worldwide. Thus, new and novel therapeutic strategies are urgently needed. Mitochondria of cardiomyocytes generate ATP that is needed to power cardiac contraction. Mitochondrial-derived ATP activate myosin ATPase at the sarcomere and the sarcoplasmic reticular (SR) ATPase Ca pump, both which intersect with Ca during contraction. Failure to maintain the relationship between mitochondria and SR can lead to cardiomyocyte dysfunction and heart failure. Here, we discuss recent discoveries that reveal Ca transport via the voltage dependent anion channel (VDAC) into the mitochondria can favorably impact cardiac contraction and prevent cardiac arrhythmias. In a broader view, discussion of the opening of a new era for HF therapeutics that will address the sarcomere, SR and mitochondria as a functional unit.
尽管有越来越多的成功疗法，心力衰竭仍然是全球范围内最常见的死亡和残疾原因。因此，迫切需要新的和新颖的治疗策略。心肌细胞的线粒体产生 ATP，这是心脏收缩所需的能量。线粒体衍生的 ATP 激活肌球蛋白 ATP 酶在肌节和肌浆网（SR）ATP 酶 Ca 泵，这两者在收缩过程中与 Ca 交叉。不能维持线粒体和 SR 之间的关系会导致心肌细胞功能障碍和心力衰竭。在这里，我们讨论了最近的发现，这些发现揭示了通过电压依赖性阴离子通道（VDAC）将 Ca 转运到线粒体中可以有利地影响心脏收缩并预防心律失常。从更广泛的角度来看，讨论了 HF 治疗学的新时代的开启，将把肌节、SR 和线粒体作为一个功能单元来处理。
