Endophilin B1 is essential for maintaining cardiac function by regulating mitocytosis.

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.