PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes

作者全名："Liu, Huiwen; Sun, Yanting; Xu, Hao; Tan, Bin; Yi, Qin; Tian, Jie; Zhu, Jing"

作者地址："[Liu, Huiwen; Sun, Yanting; Tan, Bin; Yi, Qin; Zhu, Jing] Chongqing Med Univ, Dept Pediat, Res Inst, Childrens Hosp, Chongqing 400014, Peoples R China; [Liu, Huiwen; Sun, Yanting; Xu, Hao; Tan, Bin; Yi, Qin; Tian, Jie; Zhu, Jing] Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China; [Xu, Hao] Chongqing Med Univ, Dept Clin Lab, Childrens Hosp, Chongqing 400014, Peoples R China; [Tian, Jie] Chongqing Med Univ, Dept Cardiovasc Internal Med, Childrens Hosp, Chongqing 400014, Peoples R China"

通信作者："Zhu, J (通讯作者)，Chongqing Med Univ, Dept Pediat, Res Inst, Childrens Hosp, Chongqing 400014, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001034699400001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：10

期号：5

开始页：2151

结束页：2166

文献类型：Article

关键词：hiPSCs; Maturation; Mitochondrial quality; PINK1

摘要："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. PTENinduced 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"

基金机构："National Natural Sci- ence Foundation of China [81970244]; General Basic Research Project from the Ministry of Education Key Labo- ratory of Child Development and Disorders, China [GBRP-202108]"

基金资助正文："Funding This research was supported by the National Natural Sci- ence Foundation of China (No.81970244) and General Basic Research Project from the Ministry of Education Key Labo- ratory of Child Development and Disorders, China (No. GBRP-202108) ."