PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes
作者机构:Department of Pediatric Research InstituteChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of PediatricsChongqing 400014China Department of Clinical LaboratoryChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Department of Cardiovascular(Internal Medicine)Children's Hospital of Chongqing Medical UniversityChongqing 400014China
出 版 物:《Genes & Diseases》 (基因与疾病(英文))
年 卷 期:2023年第10卷第5期
页 面:2151-2166页
核心收录:
学科分类:1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学]
基 金:supported by the National Natural Science Foundation of China(No.81970244) General Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders,China(No.GBRP-202108)
主 题:hiPSC-CMs 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 ***,the immature phenotype of these cells limits their clinical *** maturation is accompanied by changes in mitochondrial ***-induced putative kinase 1(PINK1)has been linked to mitochondrial quality ***,whether the changes in mitochondrial quality in hiPSC-CMs are associated with PINK1,and the impact of PINK1 on hiPSC-CMs development are not *** this study,we found that knockdown of PINK1 in hiPSC-CMs resulted in mitochondrial fragmentation and impaired mitochondrial functions such as mitophagy and mitochondrial ***1 deletion also inhibited the maturation of hiPSC-CMs,reverting them to a naive structural and functional *** 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 *** conclusion,PINK1 regulates the mitochondrial structure and function of hiPSC-CMs,and is essential for the maturation of hiPSC-CMs.