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.

中文翻译：

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MTCH2介导的线粒体融合驱动器从胚胎干细胞中的幼稚多能性退出。

线粒体动力学及其分子调节剂的作用在幼稚到初次启动的多能细胞相互转化过程中仍然是未知的。在这里，我们报道线粒体MTCH2是线粒体融合的调节剂，对于从幼稚到初免的小鼠胚胎干细胞（ESC）相互转化至关重要。在这种相互转换过程中，野生型ESC延长了线粒体的长度，并稍微改变了谷氨酰胺的利用率。相反，MTCH2 ^-/-ESC不能延长其线粒体并改变其新陈代谢，无法维持高水平的组蛋白乙酰化和幼稚的多能性标记物的表达。重要的是，通过亲融合蛋白线粒体融合蛋白（MFN）2或由亲裂变蛋白dynamin上相关的蛋白质的显性失活形式（DRP）1足以驱动从两个MTCH2的幼稚的多能性的出口强制线粒体伸长^{- / -}和野生型ESC。两者合计，我们的数据表明，由MTCH2支配的线粒体伸长起着至关重要的作用，并构成了从幼稚到原始的多能性小鼠ESC相互转化的早期驱动力。