Scientists found that a protein called DHHC‑1 helps keep another protein, CED‑1, stable so that dead cells can be cleared in tiny worms. Without DHHC‑1, CED‑1 levels drop and dead cells build up, but adding extra CED‑1 can fix the problem. This work shows that a chemical modification called palmitoylation protects CED‑1 from being broken down.

Dysregulation of apoptotic cell clearance is implicated in various diseases, including neurodegeneration and cancer. The phagocytic receptor CED-1 mediates the recognition of apoptotic cells by phagocytes and serves as a critical molecule for their clearance in C. elegans. However, the mechanisms ensuring the maintenance of optimal CED-1 protein levels for effective phagocytic function remain unclear. This study reveals that palmitoylation contributes to the clearance of apoptotic cells and identifies the palmitoyltransferase DHHC-1 as a key regulator of CED-1 protein levels in this process. The deletion of dhhc-1 led to a significant reduction in CED-1 protein levels, while its transcription was unaffected. Further analysis demonstrated that the absence of dhhc-1 resulted in a marked increase in the number of apoptotic cells, whereas overexpression of CED-1 restored this phenotype. Moreover, we found that DHHC-1 may stabilize CED-1 protein levels by preventing its degradation via the lysosomal and proteasomal pathways. Collectively, our findings reveal that DHHC-1 plays a vital role in the clearance of apoptotic cells by regulating CED-1 protein stability, underscoring the potential of targeting palmitoylation pathways in therapeutic strategies for diseases associated with defective apoptotic cell clearance.