PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2023-09-01
|
| Series: | Genes and Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304222002446 |
| _version_ | 1827267313223598080 |
|---|---|
| author | Huiwen Liu Yanting Sun Hao Xu Bin Tan Qin Yi Jie Tian Jing Zhu |
| author_facet | Huiwen Liu Yanting Sun Hao Xu Bin Tan Qin Yi Jie Tian Jing Zhu |
| author_sort | Huiwen Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T00:15:00Z |
| format | Article |
| id | doaj.art-ed52fc8c95c34a11931994ba9da70c4e |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2025-03-22T04:31:45Z |
| publishDate | 2023-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-ed52fc8c95c34a11931994ba9da70c4e2024-04-28T03:19:29ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-09-0110521512166PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytesHuiwen Liu0Yanting Sun1Hao Xu2Bin Tan3Qin Yi4Jie Tian5Jing Zhu6Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, ChinaChongqing Key Laboratory of Pediatrics, Chongqing 400014, China; Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, ChinaChongqing Key Laboratory of Pediatrics, Chongqing 400014, China; Department of Cardiovascular (Internal Medicine), Children's Hospital of Chongqing Medical University, Chongqing 400014, ChinaDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China; Corresponding author. Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.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.http://www.sciencedirect.com/science/article/pii/S2352304222002446hiPSC-CMshiPSCsMaturationMitochondrial qualityPINK1 |
| spellingShingle | Huiwen Liu Yanting Sun Hao Xu Bin Tan Qin Yi Jie Tian Jing Zhu PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes Genes and Diseases hiPSC-CMs hiPSCs Maturation Mitochondrial quality PINK1 |
| title | PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes |
| title_full | PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes |
| title_fullStr | PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes |
| title_full_unstemmed | PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes |
| title_short | PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes |
| title_sort | pten induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell derived cardiomyocytes |
| topic | hiPSC-CMs hiPSCs Maturation Mitochondrial quality PINK1 |
| url | http://www.sciencedirect.com/science/article/pii/S2352304222002446 |
| work_keys_str_mv | AT huiwenliu pteninducedputativekinase1regulatesmitochondrialqualitycontrolandisessentialforthematurationofhumaninducedpluripotentstemcellderivedcardiomyocytes AT yantingsun pteninducedputativekinase1regulatesmitochondrialqualitycontrolandisessentialforthematurationofhumaninducedpluripotentstemcellderivedcardiomyocytes AT haoxu pteninducedputativekinase1regulatesmitochondrialqualitycontrolandisessentialforthematurationofhumaninducedpluripotentstemcellderivedcardiomyocytes AT bintan pteninducedputativekinase1regulatesmitochondrialqualitycontrolandisessentialforthematurationofhumaninducedpluripotentstemcellderivedcardiomyocytes AT qinyi pteninducedputativekinase1regulatesmitochondrialqualitycontrolandisessentialforthematurationofhumaninducedpluripotentstemcellderivedcardiomyocytes AT jietian pteninducedputativekinase1regulatesmitochondrialqualitycontrolandisessentialforthematurationofhumaninducedpluripotentstemcellderivedcardiomyocytes AT jingzhu pteninducedputativekinase1regulatesmitochondrialqualitycontrolandisessentialforthematurationofhumaninducedpluripotentstemcellderivedcardiomyocytes |