Mitophagy induction promotes the maturation of hiPS-derived cardiomyocytes

Mitophagy dysfunction is an important contributor to the occurrence of cardiovascular diseases. Parkin-mediated mitophagy directs perinatal cardiomyocyte metabolism maturation, but its role during the earlier stage of cardiomyocyte differentiation is not fully elucidated. Human-induced pluripotent stem cell differentiated cardiomyocytes (hiPS-CMs) offer the possibility of investigating mitophagy in the differentiation process of cardiomyocytes in vitro. Therefore, in this study, we investigated the role of mitophagy involved in the differentiation and early development of hiPS-CMs. We found that mitophagy was impaired by Parkin knockdown, resulting in the inhibition of early differentiation and the development of hiPS-CMs. P62-mediated mitophagy inducer (PMI), a mitophagy enhancer, promotes early differentiation and development of hiPS-CMs and reduces the impairment of the differentiation and development of hiPS-CMs mediated by Parkin deletion. Furthermore, during differentiation and development, mitophagy plays an important role in maintaining the balance of mitochondrial homeostasis, reducing ROS accumulation, improving respiratory function, and promoting metabolic conversion. These results suggest that mitophagy activation promotes early differentiation and early development of hiPS-CMs.