The mitochondrial unfolded protein response inhibits pluripotency acquisition and mesenchymal-to-epithelial transition in somatic cell reprogramming

The mitochondrial unfolded protein response (UPRmt), a mitochondria-to-nucleus retrograde pathway, plays an important role in maintaining mitochondrial function under stress condition. However, its role in aging process in mammals remains poorly defined. The group from Guangzhou Institutes of Biomedicine and Health, China showed that transient UPRmt activation occurs during somatic reprogramming in mouse embryonic fibroblasts and impedes the mesenchymal-to-epithelial transition (MET), thereby inhibiting pluripotency acquisition.  Mechanistically, c-Jun as a downstream of UPRmt enhances the expression of acetyl-CoA metabolic enzymes and reduces acetyl-CoA levels, linking mitochondrial signaling to the epigenetic state of the cell and cell fate decisions.