Graphic summary of lysosome reformation.(A) ELR is regulated by PIKfyve, TRPML1, and Ca2+. PIKfyve converts PtdIns3P to PtdIns(3,5)P2, which activates TRPML1 to regulate lysosomal Ca2+ efflux required for lysosomal tubulation. (B) ALR is achieved by PtdIns(4,5)P2-, clathrin-, and AP2-mediated membrane budding on autolysosomes; KIF5B-driven elongation of membrane tubules along microtubules; dynamin 2–dependent protolysosome scission; and finally protolysosome maturation. AP4 enriches lysosomal membrane proteins for tubulation. WHAMM promotes lysosome tubulation by binding to PtdIns(4,5)P2. The sugar transporter Spinster is also involved in ALR. The generation of PtdIns(4,5)P2 from PtdIns4P is controlled by PtdIns4P 5-kinase 1B on autolysosome membranes and PtdIns4P 5-kinase 1A on protolysosomal tubules. The balance between PtdIns4P and PtdIns(4,5)P2 is also regulated by inositol polyphosphate-5-phosphatase K. Spastizin and spatacsin form a complex to promote tubule initiation on the autolysosome. (C) PLR is regulated by PIKfyve, TRPML1, and amino acid transporters (e.g., SLC-36.1/SLC36A1-4 and LAAT-1/PQLC2). PIKfyve probably regulates the activity of these lysosomal transporters through PtdIns(3,5)P2 to promote lysosome tubulation from phagolysosomes.
Figure 2.

Graphic summary of lysosome reformation. (A) ELR is regulated by PIKfyve, TRPML1, and Ca2+. PIKfyve converts PtdIns3P to PtdIns(3,5)P2, which activates TRPML1 to regulate lysosomal Ca2+ efflux required for lysosomal tubulation. (B) ALR is achieved by PtdIns(4,5)P2-, clathrin-, and AP2-mediated membrane budding on autolysosomes; KIF5B-driven elongation of membrane tubules along microtubules; dynamin 2–dependent protolysosome scission; and finally protolysosome maturation. AP4 enriches lysosomal membrane proteins for tubulation. WHAMM promotes lysosome tubulation by binding to PtdIns(4,5)P2. The sugar transporter Spinster is also involved in ALR. The generation of PtdIns(4,5)P2 from PtdIns4P is controlled by PtdIns4P 5-kinase 1B on autolysosome membranes and PtdIns4P 5-kinase 1A on protolysosomal tubules. The balance between PtdIns4P and PtdIns(4,5)P2 is also regulated by inositol polyphosphate-5-phosphatase K. Spastizin and spatacsin form a complex to promote tubule initiation on the autolysosome. (C) PLR is regulated by PIKfyve, TRPML1, and amino acid transporters (e.g., SLC-36.1/SLC36A1-4 and LAAT-1/PQLC2). PIKfyve probably regulates the activity of these lysosomal transporters through PtdIns(3,5)P2 to promote lysosome tubulation from phagolysosomes.

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