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. 2009 Apr;5(3):385-7.
doi: 10.4161/auto.5.3.7699. Epub 2009 Apr 23.

Double duty of Atg9 self-association in autophagosome biogenesis

Congcong He  1 , Misuzu Baba, Daniel J Klionsky
Affiliations

Double duty of Atg9 self-association in autophagosome biogenesis

Congcong He et al. Autophagy. 2009 Apr.

Abstract

The understanding of the membrane flow process during autophagosome formation is essential to illuminate the role of autophagy under various disease-causing conditions. Atg9 is the only identified integral membrane protein required for autophagosome formation, and it is thought to cycle between the membrane sources and the phagophore assembly site (PAS). Thus, Atg9 may play an important role as a membrane carrier. We report the self-interaction of Atg9 and generate an Atg9 mutant that is defective in this interaction. This mutation results in abnormal autophagy, due to altered phagophore formation as well as inefficient membrane delivery to the PAS. Based on our analyses, we discuss a model suggesting dual functions for the Atg9 complex: by reversibly binding to another Atg9 molecule, Atg9 can both promote lipid transport from the membrane origins to the PAS, and also help assemble an intact phagophore membrane.

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Figures

Figure 1
Figure 1
The loss-of-self-interaction mutant partially localizes to mitochondria. atg9Δ cells expressing plasmid-borne CUP1 promoter-driven wild-type Atg9-GFP or Atg9Δ766-770-GFP were cultured to mid-log phase and stained with Mitofluor Red 589 before imaging by fluorescence microscopy. DIC, differential interference contrast.
Figure 2
Figure 2
Possible roles of Atg9 self-association during autophagosome formation. Atg9 forms clusters on the surface of membrane sources through self-interaction, which promotes its trafficking to the PAS. Regulation of assembly and disassembly of the Atg9 complex by additional components allows the Atg9-containing vesicles to fuse with the existing phagophore membrane, which leads to phagophore expansion.
See this image and copyright information in PMC

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References

    1. Mizushima N, Yamamoto A, Hatano M, Kobayashi Y, Kabeya Y, Suzuki K, et al. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol. 2001;152:657–68. - PMC - PubMed
    1. Reggiori F, Shintani T, Nair U, Klionsky DJ. Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts. Autophagy. 2005;1:101–9. - PMC - PubMed
    1. Juhasz G, Neufeld TP. Autophagy: a forty-year search for a missing membrane source. PLoS Biol. 2006;4:36. - PMC - PubMed
    1. Young ARJ, Chan EYW, Hu XW, Köchl R, Crawshaw SG, High S, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006;119:3888–900. - PubMed
    1. Monastyrska I, He C, Geng J, Hoppe AD, Li Z, Klionsky DJ. Arp2 links autophagic machinery with the actin cytoskeleton. Mol Biol Cell. 2008;19:1962–75. - PMC - PubMed

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