Figure 10.

A working model for PTP4A2-mediated VCP p-Tyr805 dephosphorylation, ELDR complex formation, and damaged lysosome clearance. (A). VCP is localized in the cytosol in the resting state, while PTP4A2 is a lysosomal resident protein. (B). Lysosomal damage triggers extensive ubiquitination of lysosomal proteins, which recruit VCP from the cytosol to damaged lysosomes, where PTP4A2 dephosphorylates the lysosomal translocated VCP to facilitate the ELDR complex assembly on the damaged lysosomes (C). The ELDR complex promotes K48 conjugates removal, leading to successful autophagosome formation and damaged lysosome clearance.