ORIGINAL RESEARCH article
Front. Genet.
Sec. Cytogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1610008
This article is part of the Research TopicMitochondrial Pathophysiology in Cardiomyopathy and Cardiac SenescenceView all 3 articles
S100A10 Knockdown Exacerbates Phenylephrine-Induced Cardiomyocyte Hypertrophy via Modulating Mitochondrial Oxidative Phosphorylation
Provisionally accepted
Feixue Xu1,2Yajie Chen1,2
Man Xu1,2Dan Li1,2Yinshan Lu2Meng Zhang1,2Jiahao Li1,2Wanyi Li1,2
Yingying Guo1,2*- 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
- 2Hubei Key Laboratory of Metabolic and Chronic Diseases,, Wuhan, 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
Background: Mitochondrial dysfunction is a well-established hallmark of pathological cardiac hypertrophy, though its underlying mechanisms are not fully understood. S100A10, a calcium-binding protein, participates in diverse cellular processes, including the regulation of mTOR signaling and mitochondrial function. This study aims to investigate the role and mechanistic basis of S100A10 in phenylephrine (PE)-induced cardiomyocyte hypertrophy. Methods: Primary neonatal rat cardiomyocytes (NRVMs) were treated with phenylephrine (PE) to induce hypertrophy. S100A10 expression was modulated by siRNA knockdown. The interaction between S100A10 and ANXA2 was confirmed by co-immunoprecipitation. mTOR pathway activation was analyzed by Western blotting. Mitochondrial function was assessed by measuring the expression of electron transport chain complexes, mitochondrial membrane potential using JC-1 staining, and mitochondrial oxidative stress using MitoSOX. Results: S100A10 expression was significantly upregulated in hypertrophic murine hearts. We further demonstrated that S100A10 interacts with ANXA2 to activate the mTOR/4E-BP signaling pathway. Knockdown of S100A10 in NRVMs suppressed the expression of mitochondrial respiratory chain proteins, impaired oxidative phosphorylation activity, and reduced mitochondrial membrane potential and ATP production. Conclusion: These findings indicate that downregulation of S100A10 exacerbates PE-induced cardiomyocyte hypertrophy and uncover a novel function of S100A10 in modulating mitochondrial respiratory chain protein levels, potentially through the mTOR/4E-BP pathway. This may provide a theoretical basis for future therapeutic strategies.
Keywords: cardiomyocyte hypertrophy, S100A10, AnxA2, mTOR/4E-BP signaling pathway, Mitochondria
Received: 11 Apr 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Xu, Chen, Xu, Li, Lu, Zhang, Li, Li and Guo. 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: Yingying Guo, 2019103020018@whu.edu.cn
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.