Autophagy is a process by which a cell degrades cytoplasmic components such as organelles. It may be induced by stress, over-crowding, or starvation conditions in addition to its role in homeostasis. C. elegans
bec-1 is the ortholog of beclin1/Atg6/Vps30 in mammals and yeast, an important regulator of autophagy. Yeast Atg6/Vps30p was identified in a genetic screen for mutants that are starvation sensitive or defective in vacuolar protein sorting. Human Beclin 1 was identified as a protein interacting with the anti-apoptotic protein Bcl-2 in a yeast two-hybrid assay and is monoallelically deleted in up to 75% of various human cancers. Therefore, any insights on the function of
bec-1 and autophagy in C. elegans will likely shed light on the role of autophagy in tumorigenesis in humans. We have established C. elegans as a multicellular genetic model system to study the role of BEC-1 (the ortholog of Atg6/Vps30/Beclin 1) in development. We and others have found that
bec-1 functions in various fundamental biological processes, including survival, longevity, fat accumulation, dauer and reproductive development. A complete loss of function mutation of C. elegans
bec-1(
ok691) is lethal. We have isolated two mutants that suppress the
bec-1 dependent lethality and named these mutants
sub-1 and
sub-2 (suppressor of
bec-1 lethality). Interestingly, these two mutations also suppress the decrease in fat accumulation observed in
bec-1 homozygous mutant animals, as well as the shortening of lifespan associated with heterozygous
bec-1 mutants. Using single nucleotide polymorphism (SNP) mapping, we have mapped
sub-1 to a small interval on chromosome X, and
sub-2 to a small interval on chromosome IV. We will report on the molecular and genetic characterization of the
sub-1 and
sub-2 suppressor mutations.