MCU overexpression evokes disparate dose-dependent effects on mito-ROS and spontaneous Ca<sup>2+</sup> release in hypertrophic rat cardiomyocytes
Shanna Hamilton, Radmila Terentyeva, Fruzsina Perger, Benjamín Hernández Orengo, Benjamin Martin, Matthew W. Gorr, Andriy E. Belevych, Richard Clements, Sándor Györke, Dmitry Terentyev
Abstract
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.