Quantitative proteomic and phosphoproteomic analysis reveal the relationship between mitochondrial dysfunction and cytoskeletal remodeling in hiPSC-CMs deficient in PINK1.
Quantitative proteomic and phosphoproteomic analysis reveal the relationship between mitochondrial dysfunction and cytoskeletal remodeling in hiPSC-CMs deficient in PINK1.
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定量蛋白质组学和磷酸化蛋白质组学分析揭示了 PINK1 缺陷的 hiPSC-CM 中线粒体功能障碍与细胞骨架重塑之间的关系。
DOI：
10.1186/s12967-023-04467-y
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发表时间：
2023-08-30
影响因子：
7.4
通讯作者：
Zhu, Jing
中科院分区：
文献类型：
--
作者：
Liu, Huiwen;Wang, Li;Xu, Hao;Tan, Bin;Yi, Qin;Deng, Hongrong;Chen, Yunxia;He, Bolin;Tian, Jie;Zhu, Jing
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12967-023-04467-y.
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影响因子：
6
作者：
García-Bartolomé A;Peñas A;Illescas M;Bermejo V;López-Calcerrada S;Pérez-Pérez R;Marín-Buera L;Domínguez-González C;Arenas J;Martín MA;Ugalde C
通讯作者：
Ugalde C
DOI：
10.1126/science.aad2459
发表时间：
2015-12-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gong G;Song M;Csordas G;Kelly DP;Matkovich SJ;Dorn GW 2nd
通讯作者：
Dorn GW 2nd
影响因子：
7.3
作者：
Basit, Farhan;de Vries, I. Jolanda M.
通讯作者：
de Vries, I. Jolanda M.
影响因子：
4
作者：
Heeman, Bavo;Van den Haute, Chris;Baekelandt, Veerle
通讯作者：
Baekelandt, Veerle
影响因子：
5.3
作者：
Gilquin, Benoit;Taillebourg, Emmanuel;Baudier, Jacques
通讯作者：
Baudier, Jacques