Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have attracted attention in the field of regenerative medicine due to their potential ability to repair damaged hearts. However

the immature phenotype of these cells limits their clinical application. Cardiomyocyte maturation is accompanied by changes in mitochondrial quality. PTEN-induced putative kinase 1 (PINK1) has been linked to mitochondrial quality control. However

whether the changes in mitochondrial quality in hiPSC-CMs are associated with PINK1

and the impact of PINK1 on hiPSC-CMs development are not clear. In this study

we found that knockdown of PINK1 in hiPSC-CMs resulted in mitochondrial fragmentation and impaired mitochondrial functions such as mitophagy and mitochondrial biogenesis. PINK1 deletion also inhibited the maturation of hiPSC-CMs

reverting them to a naive structural and functional state. We found that restoring the mitochondrial structure did not completely rescue the mitochondrial dysfunction caused by PINK1 deletion

while activation of PINK1 kinase activity using kinetin promoted mitochondrial fusion

increased the mitochondrial membrane potential and ATP production

and maintained the development and maturation of hiPSC-CMs. In conclusion

PINK1 regulates the mitochondrial structure and function of hiPSC-CMs

and is essential for the maturation of hiPSC-CMs.