Wang Cao, Zhu Fuxing, Zhou Lan, Zhang Situo, Wang Ruiqi, Tian Hui, Zhang Bosong, Wu Jiahui, Xu Xiang, Jiang Ruixian, Hou Xiaolu, Liu Jian, Tian Weiming
School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150080, China.
The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, 150001, China, Harbin.
Commun Biol. 2025 May 9;8(1):722. doi: 10.1038/s42003-025-08139-z.
Targeting the balance of mitochondrial fission and fusion can effectively alleviate the cardiac energy supply efficiency, to restore cardiac systolic dysfunction and reduce mortality. We previously found that Klf7 is closely related to cardiac energy metabolism. Here we generated cardiomyocyte-specific Klf7 knockout and overexpression mice that underwent myocardial infarction (MI) surgery. Klf7 expression increased in the ischemic myocardium of mice, and cardiomyocyte-specific knockout Klf7 significantly lowered the mortality of MI-inflicted mice and improved ATP insufficiency in MI. Subsequently, Klf7 overexpression aggravated adverse cardiac remodeling and mitochondrial fission and fusion imbalance after MI. Our results also demonstrated that Klf7 inhibited mitochondrial fusion and promoted mitochondrial fission by targeting prohibitin 2 (Phb2) and mitofusin 2 (Mfn2). Our study revealed a crucial role in upholding the overall balance of mitochondrial fission and fusion during MI. Furthermore, our findings indicated that the Klf7/Mfn2/Phb2 axis holds promise as a potential target for therapeutic interventions of MI.
靶向线粒体分裂与融合的平衡可有效改善心脏能量供应效率,恢复心脏收缩功能障碍并降低死亡率。我们之前发现Klf7与心脏能量代谢密切相关。在此,我们构建了心肌梗死(MI)手术的心肌细胞特异性Klf7基因敲除和过表达小鼠。小鼠缺血心肌中Klf7表达增加,心肌细胞特异性敲除Klf7可显著降低MI所致小鼠的死亡率,并改善MI中的ATP不足。随后,Klf7过表达加重了MI后的不良心脏重塑以及线粒体分裂与融合失衡。我们的结果还表明,Klf7通过靶向抑制素2(Phb2)和线粒体融合蛋白2(Mfn2)来抑制线粒体融合并促进线粒体分裂。我们的研究揭示了其在维持MI期间线粒体分裂与融合的整体平衡中起关键作用。此外,我们的研究结果表明,Klf7/Mfn2/Phb2轴有望成为MI治疗干预的潜在靶点。