SaPosin-like protein SPP-10 promotes apoptotic cell degradation in Caenorhabditis elegans

Apoptotic cell clearance is essential for maintaining tissue homeostasis and preventing inflammation. While the involvement of certain lysosomal proteins in apoptotic cell clearance has been established, the roles of other lysosome-associated proteins remain unclear. Using genome-wide RNAi screening of lysosomal genes in Caenorhabditis elegans and tissue-specific analysis, we identified 14 lysosome-associated proteins crucial for apoptotic cell clearance, with the SaPosin-like protein SPP-10 being a key factor. The present study demonstrated that spp-10 defects significantly prolonged apoptotic cell persistence. Further investigations revealed that loss of spp-10 causes excessive accumulation of LAAT-1 and NUC-1 on phagolysosomes and sustained phagosomal acidification, which in turn impairs phagosomal degradation. The mammalian homolog of PSAP, whose knockdown reduces efferocytosis in mammalian cells, demonstrates that its function is evolutionarily conserved. Our findings reveal the essential role of spp-10 in apoptotic cell clearance and suggest that targeting lysosomal pathways may be a potential therapeutic strategy for diseases characterized by defective efferocytosis.