Increased RyR2 activity is exacerbated by calcium leak-induced mitochondrial ROS.

ABSTRACT: Cardiac disease is associated with deleterious emission of mitochondrial reactive oxygen species (mito-ROS), as well as enhanced oxidation and activity of the sarcoplasmic reticulum (SR) Ca²⁺ release channel, the ryanodine receptor (RyR2). The transfer of Ca²⁺ from the SR via RyR2 to mitochondria is thought to play a key role in matching increased metabolic demand during stress. In this study, we investigated whether augmented RyR2 activity results in self-imposed exacerbation of SR Ca²⁺ leak, via altered SR-mitochondrial Ca²⁺ transfer and elevated mito-ROS emission. Fluorescent indicators and spatially restricted genetic ROS probes revealed that both pharmacologically and genetically enhanced RyR2 activity, in ventricular myocytes from rats and

SUBMITTER: Hamilton S 

PROVIDER: S-EPMC7244455 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature