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Fatty acid synthesis is critical for stem cell pluripotency via promoting mitochondrial fission
Author(s) -
Wang Lihua,
Zhang Tong,
Wang Lin,
Cai Yongping,
Zhong Xiuying,
He Xiaoping,
Hu Lan,
Tian Shengya,
Wu Mian,
Hui Lijian,
Zhang Huafeng,
Gao Ping
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695417
Subject(s) - biology , reprogramming , induced pluripotent stem cell , microbiology and biotechnology , mitochondrial fission , embryonic stem cell , cell potency , stem cell , mitochondrion , biochemistry , cell , gene
Pluripotent stem cells are known to display distinct metabolic phenotypes than their somatic counterparts. While accumulating studies are focused on the roles of glucose and amino acid metabolism in facilitating pluripotency, little is known regarding the role of lipid metabolism in regulation of stem cell activities. Here, we show that fatty acid ( FA ) synthesis activation is critical for stem cell pluripotency. Our initial observations demonstrated enhanced lipogenesis in pluripotent cells and during cellular reprogramming. Further analysis indicated that de novo FA synthesis controls cellular reprogramming and embryonic stem cell pluripotency through mitochondrial fission. Mechanistically, we found that de novo FA synthesis regulated by the lipogenic enzyme ACC 1 leads to the enhanced mitochondrial fission via (i) consumption of AcCoA which affects acetylation‐mediated FIS 1 ubiquitin–proteasome degradation and (ii) generation of lipid products that drive the mitochondrial dynamic equilibrium toward fission. Moreover, we demonstrated that the effect of Acc1 on cellular reprogramming via mitochondrial fission also exists in human iPSC induction. In summary, our study reveals a critical involvement of the FA synthesis pathway in promoting ESC pluripotency and iPSC formation via regulating mitochondrial fission.