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.

人类诱导多能干细胞来源的心肌细胞（hiPSC-CM）由于其修复受损心脏的潜在能力而引起了再生医学领域的关注。然而，这些细胞的不成熟表型限制了它们的临床应用。心肌细胞的成熟伴随着线粒体质量的变化。PTEN 诱导的推定激酶 1 (PINK1) 与线粒体质量控制有关。然而，hiPSC-CM 中线粒体质量的变化是否与 PINK1 相关，以及 PINK1 对 hiPSC-CM 发育的影响尚不清楚。在这项研究中，我们发现 hiPSC-CM 中 PINK1 的敲低会导致线粒体断裂并损害线粒体功能，例如线粒体自噬和线粒体生物合成。PINK1 缺失还抑制 hiPSC-CM 的成熟，使它们恢复到原始的结构和功能状态。我们发现，恢复线粒体结构并不能完全挽救PINK1缺失引起的线粒体功能障碍，而使用激动素激活PINK1激酶活性可以促进线粒体融合，增加线粒体膜电位和ATP产生，维持hiPSC-CM的发育和成熟。 。总之，PINK1 调节 hiPSC-CM 的线粒体结构和功能，并且对于 hiPSC-CM 的成熟至关重要。