Mitochondrial metabolism transition cooperates with nuclear reprogramming during induced pluripotent stem cell generation
Mitochondrial metabolism transition cooperates with nuclear reprogramming during induced pluripotent stem cell generation
复制标题
诱导多能干细胞生成过程中线粒体代谢转变与核重编程相配合
DOI：
10.1016/j.bbrc.2012.12.148
复制
发表时间：
2013-02-22
影响因子：
3.1
通讯作者：
Liu, Xingguo
中科院分区：
文献类型：
--
作者：
Liu, Wenbo;Long, Qi;Liu, Xingguo
诱导多能干细胞（iPSC）在再生医学方面具有巨大的临床潜力。许多工作已经完成，以研究其产生的机制，集中在细胞核。然而，特定的细胞器，特别是线粒体在核重编程的潜在机制中的作用仍不清楚。在这项研究中，我们试图确定线粒体代谢转换在核重编程中的作用。我们发现，线粒体嵴在iPSCs中已经重塑。iPSC的生成效率显著降低通过下调线粒体内膜蛋白（IMMT），其调节线粒体嵴的形态。此外，具有氧化磷酸化（OXPHOS）优势的细胞比正常细胞具有更高的重编程效率，并且糖酵解中间产物乳酸增强了iPSCs生成的效率。我们的研究结果表明，线粒体嵴的重塑与iPSCs的产生耦合，表明线粒体代谢转换在核重编程中起着重要作用。(C)2013 Elsevier Inc. All rights reserved.
Induced pluripotent stem cells (iPSCs) hold great clinical potential for regenerative medicine. Much work has been done to investigate the mechanisms of their generation, focusing on the cell nucleus. However, the roles of specific organelles and in particular mitochondria in the potential mechanisms of nuclear reprogramming remain unclear. In this study, we sought to determine the role of mitochondrial metabolism transition in nuclear reprogramming. We found that the mitochondrial cristae had remodeled in iPSCs. The efficiency of iPSC generation was significantly reduced by down-regulation of mitochondrial inner membrane protein (IMMT), which regulates the morphology of mitochondrial cristae. Moreover, cells with the oxidative phosphorylation (OXPHOS) advantage had higher reprogramming efficiency than normal cells and the glycolysis intermediate lactic acid enhanced the efficiency of iPSCs generation. Our results show that the remodeling of mitochondrial cristae couples with the generation of iPSCs, suggesting mitochondrial metabolism transition plays an important role in nuclear reprogramming. (C) 2013 Elsevier Inc. All rights reserved.