细胞器之间的钙信号异常,如肌浆网(SR),线粒体和溶酶体是心脏疾病的关键特征。钙作为第二信使介导细胞层间的串扰,对维持心肌细胞功能至关重要。
本文研究了与参与细胞间钙信号传导的钙通道和转运蛋白相关的现有文献。SR钙释放通道ryanodine受体2型(RyR2)和肌醇1,4,5-三磷酸受体(IP3R),和钙转运蛋白SR/ER-ATP酶2a(SERCA2a)被照亮。线粒体电压依赖性阴离子通道(VDAC)的作用,线粒体Ca2+单向转运复合物(MCUC),和溶酶体H+/Ca2+交换体,两个孔隙通道(TPC),讨论了瞬时受体电位粘磷脂(TRPML)。此外,最近的研究表明,钙介导的SR之间的串扰,线粒体,和溶酶体以及这种串扰在心脏疾病中的失调被置于聚光灯下。
通过RyR2增强SR钙释放,通过SERCA2a降低SR再摄取,VDAC和MCUC介导的线粒体钙摄取增加,通过溶酶体TPC和TRPML增强的溶酶体钙释放都可能导致引起心脏病的异常钙稳态。虽然这种串扰的机制需要进一步研究,针对这些钙通道或其组合的干预措施可能是一种有希望的治疗策略.
Abnormal calcium signaling between organelles such as the sarcoplasmic reticulum (SR), mitochondria and lysosomes is a key feature of heart diseases. Calcium serves as a secondary messenger mediating inter-organellar crosstalk, essential for maintaining the cardiomyocyte function.
This article examines the available literature related to calcium channels and transporters involved in inter-organellar calcium signaling. The SR calcium-release channels ryanodine receptor type-2 (RyR2) and inositol 1,4,5-trisphosphate receptor (IP3R), and calcium-transporter SR/ER-ATPase 2a (SERCA2a) are illuminated. The roles of mitochondrial voltage-dependent anion channels (VDAC), the mitochondria Ca2+ uniporter complex (MCUC), and the lysosomal H+/Ca2+ exchanger, two pore channels (TPC), and transient receptor potential mucolipin (TRPML) are discussed. Furthermore, recent studies showing calcium-mediated crosstalk between the SR, mitochondria, and lysosomes as well as how this crosstalk is dysregulated in cardiac diseases are placed under the spotlight.
Enhanced SR calcium release via RyR2 and reduced SR reuptake via SERCA2a, increased VDAC and MCUC-mediated calcium uptake into mitochondria, and enhanced lysosomal calcium-release via lysosomal TPC and TRPML may all contribute to aberrant calcium homeostasis causing heart disease. While mechanisms of this crosstalk need to be studied further, interventions targeting these calcium channels or combinations thereof might represent a promising therapeutic strategy.