PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes.
PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes.
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DOI：
10.1016/j.gendis.2022.08.023
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发表时间：
2023-09
期刊：
影响因子：
6.8
通讯作者：
Zhu, Jing
中科院分区：
文献类型：
--
作者：
Liu, Huiwen;Sun, Yanting;Xu, Hao;Tan, Bin;Yi, Qin;Tian, Jie;Zhu, Jing
人诱导多能干细胞来源的心肌细胞(hiPSC-CMS)因其潜在的修复受损心脏的能力而在再生医学领域引起了人们的关注。然而，这些细胞的不成熟表型限制了它们的临床应用。心肌细胞的成熟伴随着线粒体质量的变化。PTEN诱导的PINK1(PINK1)与线粒体质量控制有关。然而，HIPSC-CMS线粒体质量的变化是否与PINK1相关，以及PINK1对HIPSC-CMS发育的影响尚不清楚。在本研究中，我们发现，在hiPSC-CMS中，PINK1基因敲除导致线粒体碎裂，并损害线粒体功能，如有丝分裂和线粒体生物发生。PINK1缺失也抑制了HiPSC-CMS的成熟，使其恢复到朴素的结构和功能状态。我们发现，恢复线粒体结构并不能完全恢复PINK1缺失引起的线粒体功能障碍，而激动素激活PINK1激酶活性促进了线粒体融合，增加了线粒体膜电位和ATP产量，维持了HiPSC-CMS的发育和成熟。综上所述，PINK1调控HIPSC-CMS的线粒体结构和功能，对HIPSC-CMS的成熟至关重要。
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. 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.
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影响因子：
13.5
作者：
Mukherjee UA;Ong SB;Ong SG;Hausenloy DJ
通讯作者：
Hausenloy DJ
DOI：
10.1016/j.biocel.2015.01.020
发表时间：
2015-06-01
影响因子：
4
作者：
Iannetti, Eligio F.;Willems, Peter H. G. M.;Koopman, Werner J. H.
通讯作者：
Koopman, Werner J. H.
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