Oxidative Stress, Mitochondrial Homeostasis, and Sirtuins in Atrial Fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Yet, its treatment has serious challenges and is unsuccessful in a considerable fraction of pa-tients. One reason may be a limited understanding of the molecular mechanisms un-derlying AF. Recent studies suggest that oxidative stress is involved in AF pathogenesis. Enhanced oxidative stress is largely determined by disrupted mitochondrial homeo-stasis, as cardiomyocytes heavily rely on mitochondrial energy production and calcium transfer between mitochondria and the sarcoplasmic reticulum. Atrial fibrillation in-volves metabolic, structural, and electrical remodeling, all of which are influenced by mitochondrial mechanisms. Mitochondrial homeostasis is controlled by mitochondrial quality control (mtQC), which is a multi-pathway mechanism to maintain integrity and functionality of mitochondria. Impaired mtQC may result in disturbed mitochon-dria-related calcium handling, decreased energy production, mitochondria-related in-flammation and fibrosis, and impaired mitophagy. Sirtuins (SIRTs) are family of 7 members of histone deacetylases, which have antioxidant properties and 3 of them are localized to mitochondria. Therefore, at least some of SIRTs may ameliorate enhanced oxidative stress related to damaged mitochondria. SIRTs have shown potential to im-prove AF outcomes in studies on AF patients and animal models. Therefore, SIRTs may have a potential to ameliorate AF through decreasing oxidative stress and restoring mitochondrial homeostasis disrupted in AF. In this narrative review we provide in-formation how mitochondrial dysfunctions, expressed as the disturbance in mtQC, contributes to AF through oxidative stress, calcium handling abnormalities, energy de-ficiency, inflammation and fibrosis, and genetic changes. In addition, we presented the protective potential of sirtuins in AF.