Atg9 proteins, not so different after all

Abstract

Macroautophagy (hereafter autophagy) is a catabolic pathway present in all eukaryotic cells. The yeast Saccharomyces cerevisiae has been pivotal in the identification and characterization of the key autophagy-related (Atg) proteins, which play a central role in the generation of autophagosomes. The components of the core Atg/ATG machinery and their functions are highly conserved among species, although mammalian cells also have isoforms and auxiliary factors. Atg9/ATG9 is the only transmembrane protein that is part of the core Atg/ATG machinery, but it appears to have divergent localizations and molecular roles in yeast and mammals. A recent experimental analysis of the yeast endo-lysosomal system by the laboratory of Benjamin Glick, however, suggests a more simple organization of this membrane system. Although this study has not examined yeast Atg9, its findings place this protein in the same compartments as its mammalian counterpart. Here, we will discuss the implications of this conceptual change on the trafficking of yeast Atg9 and its function in autophagy.

Keywords: ATG9A; Atg9; endosomes; recycling endosomes; trafficking; trans-Golgi network.

Figure 1.

Atg9/ATG9A trafficking in yeast and mammalian cells. (A) Architecture of the endosomal system in mammalian cells and the major putative ATG9A sorting pathways to the PAS and phagophore membranes (red arrows). For simplicity, the potential fusion of the autophagosome with an endosome, resulting in the formation of an amphisome, is not depicted. (B) Proposed organization of the yeast endosomal system and the main Atg9 transport routes to the PAS and phagophore membranes (red arrows).