UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells
UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells
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DOI：
10.1038/emboj.2011.401
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发表时间：
2011-12-14
期刊：
影响因子：
11.4
通讯作者：
Teitell, Michael A.
中科院分区：
文献类型：
--
作者：
Zhang, Jin;Khvorostov, Ivan;Teitell, Michael A.
主要基于形态学证据，已经假设人多能干细胞（hPSC）含有不发达的、生物能量上不活跃的线粒体。相反，分化的细胞具有以氧化磷酸化为主要能量来源的分支线粒体网络。因此，线粒体在hPSC生物能量学和细胞分化中的作用仍然不确定。在这里，我们发现hPSC具有功能性呼吸复合物，能够以最大容量消耗O-2。尽管如此，hPSC中的ATP产生主要是通过糖酵解，并且ATP被F1 F0 ATP合酶消耗以部分维持hPSC线粒体膜电位和细胞活力。解偶联蛋白2（UCP 2）通过底物分流机制阻止线粒体葡萄糖氧化并促进糖酵解，从而在hPSC能量代谢中发挥调节作用。随着早期分化，hPSC增殖减慢，能量代谢降低，并且UCP 2被抑制，导致糖酵解降低和线粒体葡萄糖氧化维持或增加。异位UCP 2表达扰乱这种代谢转变并损害hPSC分化。总的来说，hPSC含有活性线粒体，并且需要UCP 2抑制以实现完全分化潜力。The EMBO Journal（2011）30，4860-4873. doi：10.1038/daj.2011.401; 2011年11月15日在线发布
It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbour a branched mitochondrial network with oxidative phosphorylation as the main energy source. A role for mitochondria in hPSC bioenergetics and in cell differentiation therefore remains uncertain. Here, we show that hPSCs have functional respiratory complexes that are able to consume O-2 at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis and ATP is consumed by the F1F0 ATP synthase to partially maintain hPSC mitochondrial membrane potential and cell viability. Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential. The EMBO Journal (2011) 30, 4860-4873. doi: 10.1038/emboj.2011.401; Published online 15 November 2011