MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells.
MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells.
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DOI：
10.1038/s41467-018-07519-w
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发表时间：
2018-12-03
影响因子：
16.6
通讯作者：
Gross A
中科院分区：
文献类型：
--
作者：
Bahat A;Goldman A;Zaltsman Y;Khan DH;Halperin C;Amzallag E;Krupalnik V;Mullokandov M;Silberman A;Erez A;Schimmer AD;Hanna JH;Gross A
线粒体动力学及其分子调节剂的作用在幼稚到引发的多能细胞相互转换过程中仍然是未知的。在这里，我们报告，线粒体MTCH 2是线粒体融合的调节器，对于小鼠胚胎干细胞（ESCs）的幼稚到引发的相互转换至关重要。在这种相互转化过程中，野生型ESC延长了它们的线粒体并略微改变了它们的谷氨酰胺利用率。相比之下，MTCH 2 −/− ESCs不能延长其线粒体并改变其代谢，保持高水平的组蛋白乙酰化和幼稚多能性标记物的表达。重要的是，通过促融合蛋白Mitofusin（MFN）2或促分裂蛋白动力蛋白相关蛋白（DRP）1的显性负性形式来增强线粒体延长足以驱动MTCH 2 −/−和野生型ESC退出幼稚多能性。总之，我们的数据表明，由MTCH 2控制的线粒体延伸在小鼠ESC的幼稚到引发的多能性相互转换中起着关键作用，并构成了早期驱动力。线粒体代谢的重编程发生在小鼠胚胎干细胞（ESC）的幼稚至引发的多能性分化期间。在这里，作者表明，线粒体MTCH 2调节线粒体融合，这种融合是幼稚到引发的多能性转换所必需的
The role of mitochondria dynamics and its molecular regulators remains largely unknown during naïve-to-primed pluripotent cell interconversion. Here we report that mitochondrial MTCH2 is a regulator of mitochondrial fusion, essential for the naïve-to-primed interconversion of murine embryonic stem cells (ESCs). During this interconversion, wild-type ESCs elongate their mitochondria and slightly alter their glutamine utilization. In contrast, MTCH2−/− ESCs fail to elongate their mitochondria and to alter their metabolism, maintaining high levels of histone acetylation and expression of naïve pluripotency markers. Importantly, enforced mitochondria elongation by the pro-fusion protein Mitofusin (MFN) 2 or by a dominant negative form of the pro-fission protein dynamin-related protein (DRP) 1 is sufficient to drive the exit from naïve pluripotency of both MTCH2−/− and wild-type ESCs. Taken together, our data indicate that mitochondria elongation, governed by MTCH2, plays a critical role and constitutes an early driving force in the naïve-to-primed pluripotency interconversion of murine ESCs. Reprogramming of mitochondria metabolism occurs during naïve to primed pluripotency differentiation in mouse embryonic stem cells (ESCs). Here the authors show that mitochondrial MTCH2 regulates mitochondrial fusion and that this fusion is required for naïve to primed pluripotency conversion
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
16.6
作者：
Maryanovich, Maria;Zaltsman, Yehudit;Gross, Atan
通讯作者：
Gross, Atan
影响因子：
64.5
作者：
Chen H;Vermulst M;Wang YE;Chomyn A;Prolla TA;McCaffery JM;Chan DC
通讯作者：
Chan DC
影响因子：
64.5
作者：
Hanna JH;Saha K;Jaenisch R
通讯作者：
Jaenisch R
影响因子：
29
作者：
Hwang, In-Young;Kwak, Sojung;Youn, Hong-Duk
通讯作者：
Youn, Hong-Duk