Role of CR6-Interacting Factor 1 (Crif1) in Cardiac Mitochondrial Structure and Stress-Induced Functional Decline

CR6-interacting factor 1 (CRIF1) is essential for the synthesis and insertion of mitochondrial oxidative phosphorylation (OXPHOS) complexes. Although Crif1 deficiency has been linked to mitochondrial dysfunction in various tissues, its role in cardiac function remains unclear. Therefore, this study aimed to investigate the role of Crif1 in regulating mitochondrial function in the heart.

To determine the role of Crif1 and examine mitochondrial dysfunction in the heart, we generated cardiac-specific Crif1 knock-down mice using a Myh6-Cre system. Mitochondrial function was assessed by measuring oxygen consumption rates. Histological and echocardiographic examinations were performed at baseline and 2 weeks after isoproterenol infusion.

Crif1 knock-down in the heart led to structural mitochondrial abnormalities and decreased maximal oxygen consumption rates in cardiomyocytes. Although cardiac-specific Crif1 knock-down resulted in mitochondrial dysfunction, the cardiac phenotype remained normal showing preserved ejection fraction (EF) and fractional shortening (FS). However, cardiac dysfunction was aggravated under isoproterenol-induced stress, resulting in a decreased EF and FS. Cardiac hypertrophy, a typical adaptive response to isoproterenol stimulation, was attenuated.

These findings suggest that Crif1 is critical for maintaining the structure and function of mitochondria in cardiomyocytes. Additionally, mitochondrial abnormalities in the heart impair stress adaptation, leading to aggravated cardiac dysfunction under stress.