Deng Jingyu, Chang Xiaoqian, Zhang Xiaomeng, Li Congye, Guo Guigao, Song Haifeng, Zheng Yangzhi, Zhang Chenhao, Yang Bo, Zhang Chujie, Xing Pingping, Zhang Zheng, Yin Tao, Tao Ling, Wang Shan
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.
Department of Cardiology, Rocket Force Characteristic Medical Center, Beijing, 100088, China.
Cell Mol Life Sci. 2025 Mar 26;82(1):130. doi: 10.1007/s00018-025-05646-4.
Endophilin B1 is a member of the Endophilin family and has been shown to be involved in apoptosis, mitochondrial morphological changes and autophagy. Although Endophilin B1 is highly expressed in the heart, its role in the maintenance of normal cardiac function and myocardial ischemia and reperfusion (I/R) injury remains unclear. Here, we found that Endophilin B1 deletion provoked spontaneous cardiac contractile dysfunction, cardiac hypertrophy and fibrosis at 16 weeks of age. Moreover, at 8 weeks of age, although spontaneous cardiac dysfunction in Endophilin B1 deletion mice had not developed, the deletion of Endophilin B1 exacerbated I/R-induced cardiac contractile dysfunction and cardiomyocyte death, whereas restoration of Endophilin B1 expression in the heart reduced I/R injury. Furthermore, we discovered that Endophilin B1 is indispensable for maintaining normal mitochondrial structure and function. In addition, we found that Endophilin B1 is localized in extracellular mitochondrion-containing vesicles and is required for mitocytosis, a process by which damaged mitochondria are disposed through extracellular vesicles. In conclusion, our study identified Endophilin B1 as an essential mitocytosis regulator for maintaining mitochondrial homeostasis and cardiac function. These findings suggest that Endophilin B1 is a novel therapeutic target for cardiac disorders such as I/R injury, myocardial infarction and heart failure.
内吞蛋白B1是内吞蛋白家族的成员，已被证明参与细胞凋亡、线粒体形态变化和自噬。尽管内吞蛋白B1在心脏中高表达，但其在维持正常心脏功能以及心肌缺血再灌注（I/R）损伤中的作用仍不清楚。在此，我们发现16周龄时内吞蛋白B1缺失会引发自发性心脏收缩功能障碍、心脏肥大和纤维化。此外，在8周龄时，尽管内吞蛋白B1缺失小鼠尚未出现自发性心脏功能障碍，但内吞蛋白B1的缺失加剧了I/R诱导的心脏收缩功能障碍和心肌细胞死亡，而心脏中内吞蛋白B1表达的恢复则减轻了I/R损伤。此外，我们发现内吞蛋白B1对于维持正常的线粒体结构和功能不可或缺。另外，我们发现内吞蛋白B1定位于含有线粒体的细胞外囊泡中，并且是线粒体胞吐作用所必需的，线粒体胞吐作用是受损线粒体通过细胞外囊泡被清除的过程。总之，我们的研究确定内吞蛋白B1是维持线粒体稳态和心脏功能的必需线粒体胞吐调节剂。这些发现表明内吞蛋白B1是I/R损伤、心肌梗死和心力衰竭等心脏疾病的新型治疗靶点。
