SCAV‐3 affects apoptotic cell degradation in Caenorhabditis elegans

As the final step in apoptosis, apoptotic cells (ACs) are swiftly removed by specialized phagocytes, such as macrophages, or nonprofessional phagocytes, such as epidermal cells. Genetic studies of model organisms such as Caenorhabditis elegans have helped to elucidate the mechanisms of AC clearance and the underlying causes of disorders related to the dysregulation of these pathways. C. elegans possesses six class B scavenger receptor homologs, but whether they affect apoptosis is unknown. Here, we show that only the loss of function of scav‐3, the C. elegans homolog of human lysosomal integral membrane protein‐2, resulted in a considerable accumulation of cell corpses, which was caused by a failure in degradation rather than engulfment. SCAV‐3 was found to be widely distributed and localized in lysosomes to maintain the integrity of the lysosomal membrane. Further study revealed that loss of scav‐3 had no effect on phagosome maturation or the recruitment of lysosomes to phagosomes carrying cell corpses. Moreover, we discovered that the hydrolytic enzymes contained in the lysosomes were reduced in phagosomes in scav‐3 mutants. Thus, hydrolases may leak from the damaged lysosome during phagolysosome formation due to the loss of scav‐3 function, which reduces lysosome digestion activity and thus directly contributes to the elimination of ACs. SCAV‐3 is widely distributed and localized in lysosomes in Caenorhabditis elegans to maintain the integrity of the lysosomal membrane. Loss of function of SCAV‐3 causes the accumulation of apoptotic cells (ACs). We propose that hydrolases may leak from the damaged lysosome in the process of phagolysosome formation in scav‐3 mutants, which leads to the accumulation of ACs.