EFHD1 ablation inhibits cardiac mitoflash activation and protects cardiomyocytes from ischemia.

Altered levels of intracellular calcium (Ca2+) are a highly prevalent feature in different forms of cardiac injury, producing changes in contractility, arrhythmias, and mitochondrial dysfunction. In cardiac ischemia-reperfusion injury, mitochondrial Ca2+ overload leads to pathological production of reactive oxygen species (ROS), activates the permeability transition, and cardiomyocyte death. Here we investigated the cardiac phenotype caused by deletion of EF-hand domain-containing protein D1 (Efhd1 −/−), a Ca2+-binding mitochondrial protein whose function is poorly understood. Efhd1 −/− mice are viable and have no adverse cardiac phenotypes. They feature reductions in basal ROS levels and mitoflash events, both important precursors for mitochondrial injury, though cardiac mitochondria have normal susceptibility to Ca2+ overload. Notably, we also find that Efhd1 −/− mice and their cardiomyocytes are resistant to hypoxic injury. [Display omitted] • EFHD1 localizes to the mitochondrial outer membrane and intermembrane space. • Efhd1 −/− mice exhibit normal cardiac function. • Efhd1 −/− mice have reduced mitochondrial Ca2+, ΔΨ, ROS, and mitoflash levels. • Efhd1 −/− mouse cardiomyocytes are resistant to ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]