The first two lineages that segregate in early mammalian embryos – the inner cell mass (ICM) and the trophectoderm (TE) – exhibit distinct metabolic profiles: ICM cells largely use glycolysis to produce ATP, whereas TE cells switch to using mitochondrial oxidative phosphorylation (OXPHOS) for enhanced ATP production. This metabolic switch is essential for development of the early embryo but how it is controlled is unclear. Here, Soumen Paul and colleagues report that the transcription factor TEAD4 plays a key role in regulating TE energy metabolism during early mouse embryo development. They first demonstrate that both mouse TE cells and trophoblast stem cells (TSCs) exhibit mitochondrial morphologies and respiration rates that are indicative of OXPHOS. Following on from this, they show that the shRNA-mediated depletion of TEAD4, a transcription factor known to be essential for TE development, results in impaired mitochondrial function and a loss of ATP production in TSCs. The authors further report that TEAD4 regulates the transcription of electron transport chain (ETC) components that are encoded by mitochondrial DNA (mtDNA). Finally, they reveal that TEAD4 localises to mtDNA and facilitates the recruitment of a mitochondria-specific RNA polymerase, POLRMT. Together, these findings suggest that a mitochondrial-associated function of TEAD4 ensures the optimal expression of ETC components and hence promotes the energy metabolism that is required for TE development.
