正常体细胞通过线粒体葡萄糖氧化磷酸化获取能量，在应急状态下，细胞质糖酵解用以补充能量，虽然它的产能效率远低于氧化磷酸化，肿瘤细胞利用它作为主要产能途径，这一现象被称为Warburg效应。新近的研究表明，这一特征性转变也存在于诱导性多潜能干细胞中，被谓之为线粒体的重编程序。它先于干细胞诱导过程中的细胞核重编程序，为干细胞诱导的先决条件。有研究显示，AMPK可以抑制Warburg效应，并有可能藉此抑制多潜能干细胞的诱导。我们的前期工作显示AMPK存在于细胞线粒体上。综合上述，我们假设，线粒体AMPK促进细胞氧化磷酸化，以此抑制线粒体的重编程序。因此，我们将检测在多潜能干细胞诱导过程中AMPK活性和在线粒体的定位变化；研究线粒体AMPK活性的改变对干细胞诱导的影响；通过下调AMPK来提高干细胞的诱导效率。该研究有助于阐述AMPK抑制多潜能干细胞的诱导机制，开拓增加诱导效率的新途径。

Under physiological conditions, glucose oxidation via mitochondrial oxidative phosphorylation is the major source of energy (ATP) for somatic cells, while glycolysis represents a supplementary approach in coping with stresses. Although ATP-generating efficiency of glycolysis is much lower than that of oxidative phosphorylation, tumor cells acquire aerobic glycolysis as the major source of energy, a phenomenon called Warburg effect and a hallmark of tumor cell metabolism. Recent studies have demonstrated that induced pluripotent stem cells (iPS) exhibit the same trait which is described as mitochondria reprogramming, an event that precedes and is required for nuclear reprogramming. The tumor suppressor AMP-activated activated protein kinase (AMPK) has been shown to inhibit the Warburg effect, possibly through which it inhibits the induction of pluripotent stem cells. Our preliminary data have demonstrated that AMPK is located at mitochondria. Based on previous studies and our preliminary findings, we hypothesize that mitochondria-associated AMPK promotes oxidative phosphorylation, thereby inhibiting mitochondria reprogramming and the induction of pluripotent stem cells. Therefore, to test this hypothesis, we will: (1) examine changes in AMPK activity and mitochondria localization during the course of stem cell induction, (2) test if AMPK regulates mitochondria reprogramming and, (3) explore if inhibition of AMPK enhances the efficiency of stem cell induction. Completion of this study will be instrumental to understanding the mechanism underlying AMPK inhibition of iPS reprograming and provide an important approach to increase the efficiency of pluripotent stem cell induction.