The major cause of metabolic syndrome and diabetes is reduced cellular performances in fuel metabolism, but the underlying pathways and mechanisms are not completely understood. Dysregulation of energy homeostasis can lead to metabolic disturbances and it predisposes diabetes, cardiovascular disease, aging, and cancer. CR6-interacting factor 1 (CRIF1) contacts coiled-coil domain that is required for both genomic stability and mitochondrial integrity. We performed this study to determine the role of CRIF1 on the mice hearts.

CRIF1-deficient mouse was embryonic lethal and we made heart specific CRIF1-deficient mouse using Cre-loxP system. We made thoracotomy and directly injected adeno-Cre virus into the heart of CRIF1-loxP mice. Beta-gal virus was used as a control.

Serial echocardiography showed decreased left ventricular ejection fraction and fractional shortening in the CRIF1-deficient mice at four and seven weeks later compared to wild type mice (p < 0.05). H&E showed increased myocardial inflammation in the CRIF1-deficient mice. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining and LC3 staining showed increased apoptosis and autophage in CRIF1-deficient mice compared with wild type (p < 0.01). Electron microscopy revealed that the mitochondria in CRIF1-deficient cardiomyocytes showed abnormal morphogenesis. For example, the cells showed excessively fragmented mitochondria, intracristal swelling, and thinning of myocardial fiber. The stability of mitochondrial complexes in CRIF1-deficient cells showed marked derangements.

CRIF1 is required for maintenance of normal mitochondrial function and modulate apoptosis and autophagy in the heart.