Myoferlin-Mediated Lysosomal Exocytosis Regulates Cytotoxicity by Phagocytes

During inflammation, phagocytesrelease digestive enzymesfrom lysosomesto 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 exocytosisby mouse phagocytes. Myoferlin is a type II transmembrane proteinwith seven C2 domainsin the cytoplasmic region. It localizes to lysosomesand mediates their fusion with the plasma membrane upon calcium stimulation. Myoferlin promotes the release of lysosomalcontents, including hydrolytic enzymes, which increase cytotoxicity. These data demonstrate myoferlin’s critical role in lysosomal exocytosisby phagocytes, providing novel insights into the mechanisms of inflammation-related cellular injuries.