Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming
Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming
复制标题
Atg5 独立的自噬调节线粒体清除，对于 iPSC 重编程至关重要
DOI：
10.1038/ncb3256
复制
发表时间：
2015-11-01
影响因子：
21.3
通讯作者：
Ding, Sheng
中科院分区：
文献类型：
--
作者：
Ma, Tianhua;Li, Jun;Ding, Sheng
诱导多能干细胞的成功产生需要在重编程过程中从线粒体氧化磷酸化到糖酵解的主要代谢转换。然而，这种代谢重编程的机制仍然难以捉摸。在这里，我们的研究结果表明，一个Atg5独立的自噬过程介导线粒体清除，一个特征事件参与代谢开关。我们发现，阻断这种自噬，而不是典型的自噬，抑制线粒体清除，反过来，防止iPSC诱导。此外，AMPK似乎是这种自噬途径的上游，并且可以被小分子靶向以调节代谢重编程期间的线粒体清除。我们的工作不仅揭示了Atg5独立的自噬对于建立多能性至关重要，而且还表明iPSC的产生和肿瘤发生具有相似的代谢开关。
Successful generation of induced pluripotent stem cells entails a major metabolic switch from mitochondrial oxidative phosphorylation to glycolysis during the reprogramming process. The mechanism of this metabolic reprogramming, however, remains elusive. Here, our results suggest that an Atg5-independent autophagic process mediates mitochondrial clearance, a characteristic event involved in the metabolic switch. We found that blocking such autophagy, but not canonical autophagy, inhibits mitochondrial clearance, in turn, preventing iPSC induction. Furthermore, AMPK seems to be upstream of this autophagic pathway and can be targeted by small molecules to modulate mitochondrial clearance during metabolic reprogramming. Our work not only reveals that the Atg5-independent autophagy is crucial for establishing pluripotency, but it also suggests that iPSC generation and tumorigenesis share a similar metabolic switch.