Atg11 tethers Atg9 vesicles to initiate selective autophagy

• Published in: PLoS biology 2019-07, Vol.17 (7), p.e3000377-e3000377
• Main Authors: Matscheko, Nena, Mayrhofer, Peter, Rao, Yijian, Beier, Viola, Wollert, Thomas
• Format: Article
• Language: English
• Subjects: Autophagosomes; Autophagosomes - metabolism; Autophagy; Autophagy (Cytology); Autophagy-Related Proteins; Autophagy-Related Proteins - chemistry; Autophagy-Related Proteins - metabolism; Binding, Competitive; Biochemistry; Biochemistry, Molecular Biology; Biology; Biology and Life Sciences; Biosynthesis; Brewer's yeast; Cargo; Cell death; Cell research; Cellular Biology; Homeostasis; Kinases; Life Sciences; Membrane Proteins; Membrane Proteins - metabolism; Membranes; Microscopy; Molecular modelling; Nucleation; Observations; Phagocytosis; Phagosomes; Physical Sciences; Protein Binding; Protein Multimerization; Proteins; Receptors; Research and Analysis Methods; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Scaffolding; Sedimentation & deposition; Sequestering; Subcellular Processes; Tethering; Tethers; Unilamellar Liposomes; Unilamellar Liposomes - metabolism; Vesicles; Vesicular Transport Proteins; Vesicular Transport Proteins - chemistry; Vesicular Transport Proteins - metabolism
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000377

Autophagy recycles cytoplasmic components by sequestering them in double membrane-surrounded autophagosomes. The two proteins Atg11 and Atg17 are scaffolding components of the Atg1 kinase complex. Atg17 recruits and tethers Atg9-donor vesicles, and the corresponding Atg1 kinase complex induces the formation of nonselective autophagosomes. Atg11 initiates selective autophagy and coordinates the switch to nonselective autophagy by recruiting Atg17. The molecular function of Atg11 remained, however, less well understood. Here, we demonstrate that Atg11 is activated by cargo through a direct interaction with autophagy receptors. Activated Atg11 dimerizes and tethers Atg9 vesicles, which leads to the nucleation of phagophores in direct vicinity of cargo. Starvation reciprocally regulates the activity of both tethering factors by initiating the degradation of Atg11 while Atg17 is activated. This allows Atg17 to sequester and tether Atg9 vesicles independent of cargo to nucleate nonselective phagophores. Our data reveal insights into the molecular mechanisms governing cargo selection and specificity in autophagy.