Myoferlin-Mediated Lysosomal Exocytosis Regulates Cytotoxicity by Phagocytes

During inflammation, phagocytes release digestive enzymes from lysosomes to degrade harmful cells such as pathogens and tumor cells. However, the molecular mechanisms regulating this process are poorly understood. In this study, we identified myoferlin as a critical regulator of lysosomal exocytosis by mouse phagocytes. Myoferlin is a type II transmembrane protein with seven C2 domains in the cytoplasmic region. It localizes to lysosomes and mediates their fusion with the plasma membrane upon calcium stimulation. Myoferlin promotes the release of lysosomal contents, including hydrolytic enzymes, which increase cytotoxicity. These data demonstrate myoferlin’s critical role in lysosomal exocytosis by phagocytes, providing novel insights into the mechanisms of inflammation-related cellular injuries.