Provincial Key Cardiovascular Research Laboratory, Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Province, Hangzhou, China.
Wenzhou Municipal Key Cardiovascular Research Laboratory, Department of Cardiology, The First Affiliated Hospital, Wenzhou Medical University, Zhejiang Province, Wenzhou, China.
J Cell Mol Med. 2021 Oct;25(20):9496-9512. doi: 10.1111/jcmm.16941. Epub 2021 Sep 26.
Store-operated Ca entry (SOCE) machinery, including Orai channels, TRPCs, and STIM1, is key to cellular calcium homeostasis. The following characteristics of mitochondria are involved in the physiological and pathological regulation of cells: mitochondria mediate calcium uptake through calcium uniporters; mitochondria are regulated by mitochondrial dynamic related proteins (OPA1, MFN1/2, and DRP1) and form mitochondrial networks through continuous fission and fusion; mitochondria supply NADH to the electron transport chain through the Krebs cycle to produce ATP; under stress, mitochondria will produce excessive reactive oxygen species to regulate mitochondria-endoplasmic reticulum interactions and the related signalling pathways. Both SOCE and mitochondria play critical roles in mediating cardiac hypertrophy, diabetic cardiomyopathy, and cardiac ischaemia-reperfusion injury. All the mitochondrial characteristics mentioned above are determinants of SOCE activity, and vice versa. Ca signalling dictates the reciprocal regulation between mitochondria and SOCE under the specific pathological conditions of cardiomyocytes. The coupling of mitochondria and SOCE is essential for various pathophysiological processes in the heart. Herein, we review the research focussing on the reciprocal regulation between mitochondria and SOCE and provide potential interplay patterns in cardiac diseases.
钙库操纵的钙内流（SOCE）机制，包括 Orai 通道、TRPC 和 STIM1，是细胞钙稳态的关键。线粒体的以下特征参与了细胞的生理和病理调节：线粒体通过钙单向转运体介导钙摄取；线粒体受线粒体动态相关蛋白（OPA1、MFN1/2 和 DRP1）调节，并通过不断的分裂和融合形成线粒体网络；线粒体通过三羧酸循环为电子传递链提供 NADH 以产生 ATP；在应激下，线粒体将产生过多的活性氧来调节线粒体-内质网相互作用和相关信号通路。SOCE 和线粒体在介导心肌肥厚、糖尿病心肌病和心肌缺血再灌注损伤中都起着关键作用。上述所有线粒体特征都是 SOCE 活性的决定因素，反之亦然。钙信号在心肌细胞特定的病理条件下决定了线粒体和 SOCE 之间的相互调节。线粒体和 SOCE 的偶联对于心脏的各种病理生理过程都是必不可少的。在此，我们综述了关于线粒体和 SOCE 之间相互调节的研究，并提供了心脏疾病中潜在的相互作用模式。
