In addition, intracellular Ca2+ leaks disturb mitochondrial function, leading to an increase in reactive oxygen species (ROS) production and impairment of energetic metabolism, resulting in the oxidation of the calcium-handling proteins, such as RyR2 and exacerbation of the Ca2+ leak, subsequently promoting the initiation and maintenance of AF. The gene discussed is RYR2; the disease is atrial fibrillation.