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Regulation of energy metabolism during early mammalian development: TEAD4 controls mitochondrial transcription.

ABSTRACT: Early mammalian development is crucially dependent on the establishment of oxidative energy metabolism within the trophectoderm (TE) lineage. Unlike the inner cell mass, TE cells enhance ATP production via mitochondrial oxidative phosphorylation (OXPHOS) and this metabolic preference is essential for blastocyst maturation. However, molecular mechanisms that regulate establishment of oxidative energy metabolism in TE cells are incompletely understood. Here, we show that conserved transcription factor TEAD4, which is essential for pre-implantation mammalian development, regulates this process by promoting mitochondrial transcription. In developing mouse TE and TE-derived trophoblast stem cells (TSCs), TEAD4 localizes to mitochondria, binds to mitochondrial DNA (mtDNA) and facilitates its transcription by recruiting mitochondrial RNA polymerase (POLRMT). Loss of TEAD4 impairs recruitment of POLRMT, resulting in reduced expression of mtDNA-encoded electron transport chain components, thereby inhibiting oxidative energy metabolism. Our studies identify a novel TEAD4-dependent molecular mechanism that regulates energy metabolism in the TE lineage to ensure mammalian development.

SUBMITTER: Kumar RP

PROVIDER: S-EPMC6198476 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Regulation of energy metabolism during early mammalian development: TEAD4 controls mitochondrial transcription.

Kumar Ram P RP Ray Soma S Home Pratik P Saha Biswarup B Bhattacharya Bhaswati B Wilkins Heather M HM Chavan Hemantkumar H Ganguly Avishek A Milano-Foster Jessica J Paul Arindam A Krishnamurthy Partha P Swerdlow Russell H RH Paul Soumen S

Development (Cambridge, England) 20181001 19

Early mammalian development is crucially dependent on the establishment of oxidative energy metabolism within the trophectoderm (TE) lineage. Unlike the inner cell mass, TE cells enhance ATP production via mitochondrial oxidative phosphorylation (OXPHOS) and this metabolic preference is essential for blastocyst maturation. However, molecular mechanisms that regulate establishment of oxidative energy metabolism in TE cells are incompletely understood. Here, we show that conserved transcription fa ...[more]

PMID: 30201685

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Regulation of energy metabolism during early mammalian development: TEAD4 controls mitochondrial transcription.

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Regulation of energy metabolism during early mammalian development: TEAD4 controls mitochondrial transcription.

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