Miro1 as a novel regulator of hypertrophy in neonatal rat cardiomyocytes.

Cardiac hypertrophy is an adaptive response to manage an excessive cardiac workload and maintain normal cardiac function. However, sustained hypertrophy leads to cardiomyopathy, cardiac failure, and death. Adrenergic receptors play a key role in regulating cardiac function under normal and pathological conditions. Mitochondria are responsible for 90% of ATP production in cardiomyocytes. Mitochondrial function is dynamically regulated by fusion and fission processes. Changes in mitochondrial dynamics and metabolism are central issues in cardiac hypertrophy. Stimulating cardiomyocytes with adrenergic agonists generates hypertrophy and increases mitochondrial fission, which in turn is associated with decreased ATP synthesis. Miro1 is a mitochondrial outer membrane protein involved in mitochondrial dynamics and transport in neurons. The objective of this work was to evaluate whether Miro1 regulates cardiomyocyte hypertrophy through changes in mitochondrial dynamics. In neonatal rat ventricular myocytes, we showed that phenylephrine induced cardiomyocyte hypertrophy and increased Miro1 mRNA and protein levels. Moreover, alpha-adrenergic stimulation provoked a mitochondrial fission pattern in the cardiomyocytes. Miro1 knockdown prevented both the cardiomyocyte hypertrophy and mitochondrial fission pattern. Our results suggest that Miro1 participates in phenylephrine-induced cardiomyocyte hypertrophy through mitochondrial fission.