Atg22 recycles amino acids to link the degradative and recycling functions of autophagy.
In response to stress conditions (such as nutrient limitation or accumulation of damaged organelles) and certain pathological situations, eukaryotic cells use autophagy as a survival mechanism. During nutrient stress the main purpose of autophagy is to degrade cytoplasmic materials within the lysosome/vacuole lumen and generate an internal nutrient pool that is recycled back to the cytosol. This study elucidates a molecular mechanism for linking the degradative and recycling roles of autophagy. We show that in contrast to published studies, Atg22 is not directly required for the breakdown of autophagic bodies within the lysosome/vacuole. Instead, we demonstrate that Atg22, Avt3, and Avt4 are partially redundant vacuolar effluxers, which mediate the efflux of leucine and other amino acids resulting from autophagic degradation. The release of autophagic amino acids allows the maintenance of protein synthesis and viability during nitrogen starvation. We propose a "recycling" model that includes the efflux of macromolecules from the lysosome/vacuole as the final step of autophagy.
Yang
Zhifen
Z
Life Sciences Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Huang
Ju
J
Geng
Jiefei
J
Nair
Usha
U
Klionsky
Daniel J
DJ
D026905:Amino Acid Transport Systems / Q000378:metabolism; D000596:Amino Acids / Q000172:deficiency / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism
C418505:ATG22 protein, S cerevisiae; D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins