Aggrephagy: lessons from C. elegans

Autophagy is a lysosome-mediated degradation process that involves the formation of an enclosed double-membrane autophagosome. Yeast genetic screens have laid the groundwork for a molecular understanding of autophagy. The process, however, exhibits fundamental differences between yeast and higher eukaryotes. Very little is known about essential autophagy components specific to higher eukaryotes. Recent studies have shown that a variety of protein aggregates are selectively removed by autophagy (a process termed aggrephagy) during Caenorhabditis elegans embryogenesis, establishing C. elegans as a multicellular genetic model to delineate the autophagic machinery. The genetic screens were carried out in C. elegans to identify essential autophagy genes. In addition to conserved and divergent homologues of yeast Atg proteins, several autophagy genes conserved in higher eukaryotes, but absent from yeast, were isolated. The genetic hierarchy of autophagy genes in the degradation of protein aggregates in C. elegans provides a framework for understanding the concerted action of autophagy genes in the aggrephagy pathway.