Quantitative proteomic and phosphoproteomic analysis reveal the relationship between mitochondrial dysfunction and cytoskeletal remodeling in hiPSC-CMs deficient in PINK1
作者全名:"Liu, Huiwen; Wang, Li; Xu, Hao; Tan, Bin; Yi, Qin; Deng, Hongrong; Chen, Yunxia; He, Bolin; Tian, Jie; Zhu, Jing"
作者地址:"[Liu, Huiwen; Wang, Li; Tan, Bin; Yi, Qin; Deng, Hongrong; Chen, Yunxia; He, Bolin; Zhu, Jing] Chongqing Med Univ, Dept Pediat Res Inst, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing, Peoples R China; [Liu, Huiwen; Wang, Li; Xu, Hao; Tan, Bin; Yi, Qin; Deng, Hongrong; Chen, Yunxia; He, Bolin; Tian, Jie; Zhu, Jing] Chongqing Med Univ, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing, Peoples R China; [Xu, Hao] Chongqing Med Univ, Childrens Hosp, Dept Clin Lab, Chongqing, Peoples R China; [He, Bolin] Chongqing Med Univ, Childrens Hosp, Dept Blood Transfus, Chongqing, Peoples R China; [Tian, Jie] Chongqing Med Univ, Dept Cardiovasc Internal Med, Childrens Hosp, Chongqing, Peoples R China"
通信作者:"Zhu, J (通讯作者),Chongqing Med Univ, Dept Pediat Res Inst, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing, Peoples R China.; Zhu, J (通讯作者),Chongqing Med Univ, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing, Peoples R China."
来源:JOURNAL OF TRANSLATIONAL MEDICINE
ESI学科分类:CLINICAL MEDICINE
WOS号:WOS:001058581200001
JCR分区:Q1
影响因子:6.1
年份:2023
卷号:21
期号:1
开始页:
结束页:
文献类型:Article
关键词:hiPSC-CMs; PINK1; Proteomic; Phosphoproteomic; Cytoskeleton; Mitochondrial; Respiratory chain
摘要:"Background Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are seed cells that can be used for alternative treatment of myocardial damage. However, their immaturity limits their clinical application. Mitochondrial development accompanies cardiomyocyte maturation, and PINK1 plays an important role in the regulation of mitochondrial quality. However, the role and mechanism of PINK1 in cardiomyocyte development remain unclear. Methods We used proteomic and phosphoproteomic to identify protein and phosphosite changes in hiPSC-CMs deficient in PINK1. Bioinformatics analysis was performed to identify the potential biological functions and regulatory mechanisms of these differentially expressed proteins and validate potential downstream mechanisms. Results Deletion of PINK1 resulted in mitochondrial structural breakdown and dysfunction, accompanied by disordered myofibrils arrangement. hiPSC-CMs deficient in PINK1 exhibited significantly decreased expression of mitochondrial ATP synthesis proteins and inhibition of the oxidative phosphorylation pathway. In contrast, the expression of proteins related to cardiac pathology was increased, and the phosphoproteins involved in cytoskeleton construction were significantly altered. Mechanistically, PINK1 deletion damaged the mitochondrial cristae of hiPSC-CMs and reduced the efficiency of mitochondrial respiratory chain assembly. Conclusion The significantly differentially expressed proteins identified in this study highlight the important role of PINK1 in regulating mitochondrial quality in hiPSC-CMs. PINK1-mediated mitochondrial respiratory chain assembly is the basis for mitochondrial function. Whereas the cytoskeleton may be adaptively altered in response to mitochondrial dysfunction caused by PINK1 deletion, inadequate energy supply hinders myocardial development. These findings facilitate the exploration of the mechanism of PINK1 in cardiomyocyte development and guide efforts to promote the maturation of hiPSC-CMs."
基金机构:We thank the Department of Pediatric Research Institute for the technical assistance provided.
基金资助正文:We thank the Department of Pediatric Research Institute for the technical assistance provided.