Atg8 controls phagophore expansion during autophagosome formation.
Autophagy is a potent intracellular degradation process with pivotal roles in health and disease. Atg8, a lipid-conjugated ubiquitin-like protein, is required for the formation of autophagosomes, double-membrane vesicles responsible for the delivery of cytoplasmic material to lysosomes. How and when Atg8 functions in this process, however, is not clear. Here we show that Atg8 controls the expansion of the autophagosome precursor, the phagophore, and give the first real-time, observation-based temporal dissection of the autophagosome formation process. We demonstrate that the amount of Atg8 determines the size of autophagosomes. During autophagosome biogenesis, Atg8 forms an expanding structure and later dissociates from the site of vesicle formation. On the basis of the dynamics of Atg8, we present a multistage model of autophagosome formation. This model provides a foundation for future analyses of the functions and dynamics of known autophagy-related proteins and for screening new genes.
Xie
Zhiping
Z
Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Nair
Usha
U
Klionsky
Daniel J
DJ
D001343:Autophagy / Q000235:genetics*; D000071190:Autophagy-Related Protein 8 Family; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008561:Membrane Fusion; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins