PHB2通过稳定TOMM40和调节线粒体形态功能稳态来保护小鼠免受压力过载诱导的心肌重塑，这一成果由武汉大学唐其柱研究团队经过不懈努力而取得。2025年7月14日出版的《中国药理学报》杂志发表了这项成果。

在这项研究中，课题组研究了PHB2在横断主动脉收缩（TAC）诱导的心脏重塑中的保护作用，特别关注其通过改善线粒体功能和减轻氧化应激来保护心脏的能力。课题组发现，在TAC小鼠心脏和Ang II（1μM）处理的心肌细胞中，PHB2的表达显著降低。心脏特异性PHB2过表达可减轻TAC诱导的心脏重塑，改善心功能并减轻肥厚。此外，PHB2过表达可有效抑制TAC小鼠心脏氧化应激，同时改善线粒体形态和内膜结构的完整性。

此外，PHB2过表达恢复了Ang II处理心肌细胞的线粒体功能，这可以通过ATP水平升高和氧化磷酸化能力增强来证明。IP-MS分析显示，PHB2直接与线粒体外膜转运蛋白40 （TOMM40）相互作用，调节线粒体功能。重要的是，沉默TOMM40消除了PHB2的保护作用。研究人员证明PHB2主要通过抑制泛素依赖性蛋白酶体降解来保持TOMM40蛋白水平。总之，该团队发现PHB2在病理应激下通过促进TOMM40稳定来保护线粒体形态功能稳态的新功能，这表明PHB2是潜在干预心脏病的有希望的治疗靶点。

研究人员表示，心肌重构是多种心血管疾病的关键病理过程，其中氧化还原失衡和线粒体生物能量扰动是关键决定因素。Prohibitin 2（PHB2）位于线粒体内膜，是线粒体稳态的关键调节因子。

附：英文原文

Title: PHB2 protects against pressure overload-induced myocardial remodeling in mice via stabilizing TOMM40 and regulating mitochondrial morphofunctional homeostasis

Author: Li, Dan, Li, Jia-hao, Guo, Ying-ying, Chen, Ya-jie, Zhang, Meng, Xu, Fei-xue, Li, Wan-yi, Tang, Qi-zhu

Issue&Volume: 2025-07-14

Abstract: Myocardial remodeling is critical pathological processes in various cardiovascular diseases, where redox imbalance and mitochondrial bioenergetic perturbations emerge as key determinants. Prohibitin 2 (PHB2), which resides in the mitochondrial inner membrane, serves as a critical regulator of mitochondrial homeostasis. In this study we investigated the protective role of PHB2 in transverse aortic constriction (TAC)-induced cardiac remodeling with a particular focus on its ability to safeguard the heart by improving mitochondrial function and alleviating oxidative stress. We revealed that PHB2 expression was significantly decreased in the heart of TAC mice and in Ang II (1μM)-treated cardiomyocytes. Cardiac-specific PHB2 overexpression mitigated TAC-induced cardiac remodeling, improving cardiac function and attenuating hypertrophy. Additionally, PHB2 overexpression effectively suppressed oxidative stress in the hearts of TAC mice, while improving mitochondrial morphology and the integrity of inner membrane structure. Furthermore, PHB2 overexpression restored mitochondrial function in Ang II-treated cardiomyocytes evidenced by elevated ATP levels and enhanced oxidative phosphorylation capacity. IP-MS analysis revealed that PHB2 directly interacted with Transporter of Outer Mitochondrial Membrane 40 (TOMM40) to regulate mitochondrial function. Importantly, silencing TOMM40 abolished the protective effects of PHB2. We demonstrated that PHB2 preserves TOMM40 protein levels predominantly through inhibition of ubiquitin-dependent proteasomal degradation. Collectively, we discover a new function of PHB2 in safeguarding mitochondrial morphofunctional homeostasis in response to pathological stress through facilitating TOMM40 stabilization, suggesting PHB2 as a promising therapeutic target for potential interventions in heart diseases.

DOI: 10.1038/s41401-025-01613-8

Source: https://www.nature.com/articles/s41401-025-01613-8