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- Title
Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming.
- Authors
Ma, Tianhua; Li, Jun; Xu, Yue; Yu, Chen; Xu, Tao; Wang, Haixia; Liu, Kai; Cao, Nan; Nie, Bao-ming; Zhu, Sai-yong; Xu, Shaohua; Li, Ke; Wei, Wan-guo; Wu, Yuzhang; Guan, Kun-liang; Ding, Sheng
- Abstract
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.
- Subjects
INDUCED pluripotent stem cells; AUTOPHAGY; OXIDATIVE phosphorylation; MITOCHONDRIAL pathology; GLYCOLYSIS
- Publication
Nature Cell Biology, 2015, Vol 17, Issue 11, p1379
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb3256