Autophagy shows its animal side

Abstract

Most autophagy genes have been discovered in the single-celled yeast Saccharomyces cerevisiae, and little is known about autophagy genes that are specific to multicellular animals. In this issue, Tian et al. (2010) now identify four new autophagy genes: one specific to the nematode Caenorhabditis elegans and three conserved from worms to mammals.

Figure 1. Genes Required for Autophagy in Animals

Autophagy degrades and recycles cytoplasmic contents. For example, during the development of Caenorhabditis elegans embryos, autophagy clears from somatic cells aggregates of proteins and RNA molecules known as P granules. Upon autophagy induction, isolation membranes nucleate at structures derived from the endoplasmic reticulum (ER) called omegasomes. As an isolation membrane expands, it engulfs P granules and then closes up to produce an autophagosome. Lysosomes fuse with the outer membrane of an autophagosome to form an autolysosome, where hydrolase enzymes degrade the inner membrane and cargo. Degraded cargo is then released into the cytosol for reuse. Using a genetic screen, Tian et al. (2010) now uncover four new genes in C. elegans (epg-2, -3, -4, and -5), which are required specifically for autophagy in animals. Whereas epg-2 is required for recognizing cargo, mutations in epg-3 and epg-4 lead to the accumulation of isolation membranes and omegasomes. Embryos with mutations in epg-5 accumulate autolysosomes that fail to degrade cargo. Strikingly, mammalian homologs of epg-3,-4, and -5 are also required for autophagy in cell cultures. VMP1 functions at an early step of autophagosome formation, whereas mEPG-5 and EI24 act at later stages.