Programmed cell death plays a key role in the development and homeostasis of multicellular organisms. Many genes have been identified that regulate cell death in C. elegans, including members of the core apoptotic pathway terminating upon the executioner gene,
ced-3. The
asp-3 gene, which encodes for an aspartyl protease, has previously been implicated in necrotic but not apoptotic cell death. Here, we present evidence of a role for
asp-3 in apoptotic programmed cell death. ASP-3 is a member of the aspartate protease family, members of which require one or more aspartic acid residues to catalyze protein cleavage. We quantified apoptotic corpses in
tm4559 an
asp-3 null mutant, and found that loss of
asp-3 decreased cell corpse number at multiple embryonic stages. Cell corpse duration was unchanged in
asp-3 mutants and these animals exhibited extra cell survival, suggesting a defect in killing rather than accelerated corpse clearance or a shift in timing of cell death. The apoptotic defect in
asp-3 mutants could be rescued by transgenic expression of
asp-3 behind its own promoter or using Pegl-1 in which the protein is expressed only in dying cells. However, if the key aspartate residue at position 279 was mutated, the transgene did not rescue. We next asked whether
asp-3 was part of the core apoptotic pathway. In a weak
ced-3 allele such as
n2438, apoptosis during embryogenesis is both decreased and delayed. In
ced-3(
n2438);
asp-3(
tm4559) double mutants, even fewer cell corpses were seen than in
ced-3(
n2438) alone, suggesting that
asp-3 acts downstream of or parallel to the
ced-3 pathway to promote cell killing. Further, ASP-3 protein levels appeared increased in
ced-3(
n2438) mutant but not in a strong
ced-3 allele such
n717, suggesting that induction of ASP-3 may modulate the killing phenotype of
ced-3 alleles. Our findings support a role for the aspartyl protease ASP-3 in apoptotic cell death. The ability of ASP-3 to be induced in weak
ced-3 alleles suggests that ASP-3 may be part of an alternative pathway that is recruited when CED-3 dependent cell death is blocked. The mammalian homolog of ASP-3, Cathepsin D, has been implicated in neurodegenerative disease. Therefore, understanding ASP-3 activity in both apoptotic and necrotic cell death may have consequences for neurodegeneration and other diseases of aging.