Key result
Moderate MCU overexpression and mito-ROS scavenging rescued cytosolic and mitochondrial Ca2+ homeostasis in hypertrophic rat cardiomyocytes, whereas high MCU overexpression was not beneficial.
Why the study?
Defective intracellular Ca2+ homeostasis and aberrant mitochondrial function are common features in cardiac disease.
In hypertrophic rat cardiomyocytes, mito-ROS scavenging and moderate MCU overexpression improve calcium homeostasis and mitochondrial ROS emission, suggesting a dose-dependent therapeutic window for MCU targeting.
Defective intracellular Ca 2+ homeostasis and aberrant mitochondrial function are common features in cardiac disease. Here, we directly compared potential benefits of mito-ROS scavenging and restoration of mito-Ca 2+ uptake by overexpressing MCU in ventricular myocytes from hypertrophic rat hearts. Experiments using novel mito-ROS and Ca 2+ biosensors demonstrated that mito-ROS scavenging rescued both cytosolic and mito-Ca 2+ homeostasis, whereas moderate and high MCU overexpression demonstrated disparate effects on mito-ROS emission, with only a moderate increase in MCU being beneficial.
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Hamilton et al. (2021) studied Hypertrophic rat hearts. MCU overexpression and mito-ROS scavenging was evaluated on Mito-ROS emission and cytosolic/mito-Ca2+ homeostasis. Moderate MCU overexpression and mito-ROS scavenging rescued cytosolic and mitochondrial Ca2+ homeostasis in hypertrophic rat cardiomyocytes, whereas high MCU overexpression was not beneficial.
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