Mucolipidosis type IV protein TRPML1-dependent lysosome formation

Lysosomes are dynamic organelles that undergo cycles of fusion and fission with themselves and with other organelles. Following fusion with late endosomes to form hybrid organelles, lysosomes are reformed as discrete organelles. This lysosome reformation or formation is a poorly understood process that has not been systematically analyzed and that lacks known regulators. In this study, we quantitatively define the multiple steps of lysosome formation and identify the first regulator of this process. Lysosomes are dynamic organelles that undergo cycles of fusion and fission with themselves and with other organelles. New lysosomes are formed or reformed through a process of budding from late endosomes/hybrid organelles, membrane extension moving the nascent lysosomes away from the late endosomes late endosomes/hybrid organelles, and scission of the connecting membrane releasing the lysosomes. We show that the Mucolipidosis type IV non-selective cation channel protein TRPML1 is required for the scission step that releases distinct lysosomes.