Langenbacher Adam D, Shimizu Hirohito, Hsu Welkin, Zhao Yali, Borges Alexandria, Koehler Carla, Chen Jau-Nian
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, United States.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, United States.
Front Physiol. 2020 Dec 23;11:617492. doi: 10.3389/fphys.2020.617492. eCollection 2020.
Mitochondrial Ca uptake influences energy production, cell survival, and Ca signaling. The mitochondrial calcium uniporter, MCU, is the primary route for uptake of Ca into the mitochondrial matrix. We have generated a zebrafish mutant that survives to adulthood and exhibits dramatic cardiac phenotypes resembling cardiomyopathy and sinus arrest. hearts contract weakly and have a smaller ventricle with a thin compact layer and reduced trabecular density. Damaged myofibrils and swollen mitochondria were present in the ventricles of mutants, along with gene expression changes indicative of cell stress and altered cardiac structure and function. Using electrocardiography, we found that hearts display conduction system defects and abnormal rhythm, with extended pauses resembling episodes of sinus arrest. Together, our findings suggest that proper mitochondrial Ca homeostasis is crucial for maintaining a healthy adult heart, and establish the mutant as a useful model for understanding the role of mitochondrial Ca handling in adult cardiac biology.
线粒体钙摄取影响能量产生、细胞存活和钙信号传导。线粒体钙单向转运体（MCU）是钙进入线粒体基质的主要途径。我们培育出了一种成年后仍存活的斑马鱼突变体，其表现出类似于心肌病和窦性停搏的显著心脏表型。突变体心脏收缩微弱，心室较小，致密层薄且小梁密度降低。突变体心室中存在受损的肌原纤维和肿胀的线粒体，同时伴有指示细胞应激以及心脏结构和功能改变的基因表达变化。通过心电图检查，我们发现突变体心脏存在传导系统缺陷和异常节律，伴有类似于窦性停搏发作的延长停顿。总之，我们的研究结果表明，适当的线粒体钙稳态对于维持健康的成年心脏至关重要，并将该突变体确立为理解线粒体钙处理在成年心脏生物学中作用的有用模型。
