Rnd3 is Essential for Mitochondrial Integrity and Function in Cardiomyocytes
Abstract
Small GTPase Rnd3 participates in a broad spectrum of pathological processes. The downregulation of Rnd3 is observed in heart failure patients, and causes cardiac dysfunction in animal models. The dysfunction of mitochondria is one of the key factors contributing to heart failure. Whether Rnd3 downregulation plays a regulatory role in mitochondrial dysfunction in the heart remains unknown. Using genetic Rnd3 haploinsufficient mice, we demonstrated for the first time to our knowledge, that the decreased expression of Rnd3 causes mitochondrial dysfunction, which results in reduced ATP production and increased generation of reactive oxygen species (ROS), and eventually cell apoptosis. We revealed the associated molecular mechanism, in which Rnd3 deficiency leads to intracellular calcium overload, and consequently increased mitochondrial calcium levels. The latter triggers mitochondrial dysfunction. Calcium uptake inhibitor Ru360 treatment partially rescues this cellular phenotype. We conclude that a normal expression level of Rnd3 is essential for mitochondrial integrity and function in the heart.
Citation
Andrade, Kelsey Colleen (2018). Rnd3 is Essential for Mitochondrial Integrity and Function in Cardiomyocytes. Master's thesis, Texas A & M University. Available electronically from https : / /hdl .handle .net /1969 .1 /173479.