title: The ATG conjugation systems are important for degradation of the inner autophagosomal membrane.
abstract: In macroautophagy, cytoplasmic contents are sequestered into the double-membrane autophagosome, which fuses with the lysosome to become the autolysosome. It has been thought that the autophagy-related (ATG) conjugation systems are required for autophagosome formation. Here, we found that autophagosomal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 17-positive autophagosome-like structures could be generated even in the absence of the ATG conjugation systems, although at a reduced rate. These syntaxin 17-positive structures could further fuse with lysosomes, but degradation of the inner autophagosomal membrane was significantly delayed. Accordingly, autophagic activity in ATG conjugation-deficient cells was strongly suppressed. We suggest that the ATG conjugation systems, which are likely required for the closure (i.e., fission) of the autophagosomal edge, are not absolutely essential for autolysosome formation but are important for efficient degradation of the inner autophagosomal membrane.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tsuboyama
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Koyama-Honda
authors.affiliation: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Sakamaki
authors.affiliation: Departments of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morishita
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. nmizu@m.u-tokyo.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
mesh_terms: D000071182:Autophagosomes / Q000378:metabolism*; D001343:Autophagy; D000071192:Autophagy-Related Protein 12 / Q000235:genetics / Q000378:metabolism*; D000071190:Autophagy-Related Protein 8 Family / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008561:Membrane Fusion; D010714:Phosphatidylethanolamines / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000378:metabolism*
chemical_list: D000071192:Autophagy-Related Protein 12; D000071190:Autophagy-Related Protein 8 Family; D010714:Phosphatidylethanolamines; D050765:Qa-SNARE Proteins; C551267:STX17 protein, human; C483858:phosphatidylethanolamine