Cardiac function in response to pressure‐overload and aging‐induced stress involves regulation of mitochondrial dynamics by the mitochondrial kinase, Pink1

Aging and hypertrophic stress are associated with cardiac dysfunction in humans. As mitochondria are important to energetics and cell survival in the heart, we employed rat neonatal cardiomyocytes (RNCs) to examine changes in mitochondrial‐related proteins. Phenylephrine treatment of RNCs resulted in increased hypertrophy and an increase in the mitochondrial fission protein, Drp1, and a decrease in the mitochondrial kinase, PTEN‐Induced Kinase 1 (Pink1). As Pink1, like Drp1, is important in regulation of mitochondrial dynamics, we studied heart function in Pink1−/− mice. Pink1−/− mice exhibited decreased ejection fraction (EF) compared with Pink1+/+ after 8 weeks with thoracic aortic constriction (TAC) to cause pressure‐overload (PO)‐induced hypertrophy. More fibrosis was also observed in the Pink1−/− compared to wild‐type (WT) mice after TAC. Interestingly, Pink1−/− mice at 6 months of age showed significant decrease in EF and an increase in left ventricular inner diameter compared with WT. Pink1−/− mice demonstrate increased Drp1 and decreased mitochondrial size as compared to WT, while WT after eight weeks of TAC show decreased Pink1 expression. Furthermore, Pink1−/− and Pink1+/+ mice provided dobutamine to increase acute energetic demand did not exhibit differences in EF or heart rate demonstrating that loss of Pink1 does not contribute directly to mitochondrial energetic potential. These data demonstrate a need for Pink1 in preserving cardiac function after aging or PO, and the mechanism involves mitochondrial dynamics, but not a direct involvement in bioenergetics.