Impaired Mitophagy: A New Potential Mechanism of Human Chronic Atrial Fibrillation

Abstract

Mitophagy is an autophagic response and plays essential roles in survival, development, and homeostasis of cells. It has been reported that mitophagic dysfunction is involved in several cardiovascular diseases. However, the effect of mitophagy on atrial fibrillation (AF) is still unknown. Therefore, we investigated the exact role of mitophagy in human chronic AF. Western blot was used to detect the protein abundance. The mitochondrial morphology and structure were observed by transmission electron microscopy. Immunofluorescent stainings were performed to analyze colocalization of mitochondria with autophagosomes or lysosomes. Totally, 43 patients with valvular heart disease undergoing cardiac surgery were selected, including 21 patients with chronic AF. Comparing with the sinus rhythm (SR) group, we found the size and number of mitochondria in atrial myocytes of patients with AF increased significantly. In addition, expression of LC3B II and LC3B II/LC3B I ratio was significantly decreased in the AF group. Moreover, the expression of p62 was markedly elevated in the AF group compared with that in the SR group. The results of immunofluorescence staining and western blot showed an enhanced expression of Cox IV in the AF group. Dual immunofluorescent stainings revealed that mitophagy defect in atrial myocytes of patients with AF resulted from dysfunction in the process of delivery of mitochondria into autophagosomes. For the first time, impaired mitophagy, during the phagocytosis of mitochondria, is associated with human chronic AF. Mitophagy could be a potential therapeutic target for AF.