Description

Macroautophagy (hereon referred as Autophagy) is a cellular housekeeping mechanism that uses a double membrane to target and engulf cell products forthe formation of autophagosomes. These double membrane organelles then fuse to lysosomes where cell products are degraded and recycled (Nakamura and Yoshimori, 2018). Reports show that autophagy plays an important role in pathogen defense, development, starvation adaptations, and aging (Mizushima et al., 2008). Identifying molecular mechanisms responsible for autophagy in mammalian cells has been possible as a result of studying model systems, such as Saccharomyces cerevisiae. Autophagy related genes (Atg) are evolutionarily conserved; therefore, research of autophagy in simpler organisms have informed the roles of Atg in mammalian cells (Ruck et al., 2011; Mercer et al., 2018; Tyler and Johnson, 2018). Analysis of autophagy mutants in C. elegansrevealed that bec-1/Atg6/Beclin 1 is essential for dauer development, a quiescent state that survives harsh conditions such as lack of nutrients, high nematode density, and high temperatures by inducing autophagy (Meléndez et al., 2003; Meléndez and Levine 2009).

To further investigate the phenotypes associated with the bec-1(ok691) mutation, we studied nematodes possessing a 3000 base pair deletion mutation (allele ok691) in the bec-1 locus (Figure 1A). Previous reports show that the bec-1(ok691) mutation is lethal, however a small proportion of homozygous bec-1(ok691) animals reach adulthood due to maternal effect, but do not reproduce due to sterility (Figure 1B, Melendez and Levine 2009). Our analysis of survival throughout adulthood shows that lifespan is significantly reduced in homozygous bec-1(ok691) mutants (Figure 1C). These nematodes do not live longer than 8 days of adulthood and 50% of animals died at day 5 of adulthood. In contrast, heterozygous bec-1(ok691) mutant lifespan is not significantly different from control animals, ruling out previously discovered haploid insufficiency effects of Beclin 1 for autophagic activity in C. elegans (Sinha and Levine, 2008). This conclusion should be considered as preliminary as we have not verified by an alternative line of investigation (e.g., a second allele or transgene rescue) that the observed phenotypes are specific to bec-1(ok691).