REVIEW article
Front. Cell Dev. Biol.
Sec. Embryonic Development
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1662431
The Role and Regulatory Mechanisms of the TCA Cycle in Early Embryonic Development
Provisionally accepted
- Gannan Medical University, Ganzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The tricarboxylic acid cycle (TCA cycle) serves as a critical metabolic hub in embryonic development. Its dynamic reprogramming not only coordinates energy supply and biosynthesis but also profoundly influences cell fate decisions through the metabolic-epigenetic coupling mechanism. This review systematically explores the TCA cycle central role in driving the adaptive metabolic changes of embryos, such as mitochondrial maturation and lineage differentiation, and precisely regulating the timing of zygotic genome activation (ZGA). It highlights how the nuclear translocation of key enzymes in the TCA cycle creates a nuclear metabolic microenvironment, which directly regulates histone modifications (acetylation, methylation) and DNA demethylation through intermediate products like Ac-CoA and α-ketoglutarate (α-KG), thereby achieving epigenetic remodeling. Additionally, the review emphasizes the pathological mechanisms by which mitochondrial dysfunction (such as insufficient ATP synthesis, abnormal metabolite accumulation, and oxidative stress imbalance) leads to developmental arrest through epigenetic disorders and DNA damage.
Keywords: TCA cycle, Embryonic Development, zygotic genome activation, Energymetabolism, nuclear localization, epigenetic modification
Received: 09 Jul 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 Lai, Gao, 赵, Liu, Gao, Yan, Zeng, Liao and Zhong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zibing Liao, Gannan Medical University, Ganzhou, China
Jianing Zhong, Gannan Medical University, Ganzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.