The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation

• Published in: The EMBO journal Vol. 20; no. 21; pp. 5971 - 5981
• Main Authors: Suzuki, Kuninori, Kirisako, Takayoshi, Kamada, Yoshiaki, Mizushima, Noboru, Noda, Takeshi, Ohsumi, Yoshinori
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2001; Nature Publishing Group UK; Springer Nature B.V; Oxford University Press
• Subjects: APG; APG gene; Apg1 protein; Apg12 protein; Apg16 protein; Apg5 protein; Apg9 protein; Aut7 protein; autophagosome; autophagosomes; Autophagy; Autophagy - physiology; Autophagy-Related Protein 5; Autophagy-Related Protein 8 Family; Autophagy-Related Proteins; Carrier Proteins; Carrier Proteins - genetics; Carrier Proteins - metabolism; cytochemistry; Fungal Proteins; Fungal Proteins - genetics; Fungal Proteins - metabolism; genes; genetic techniques and protocols; genetics; GFP; Green Fluorescent Proteins; Heat-Shock Proteins; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Luminescent Proteins; Luminescent Proteins - genetics; macroautophagy; Macromolecular Substances; membrane dynamics; Membrane Proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; metabolism; Microtubule-Associated Proteins; Microtubule-Associated Proteins - metabolism; Mutagenesis; mutants; phagocytosis; phosphatidylethanolamine; physiology; Protein Processing, Post-Translational; Protein Processing, Post-Translational - physiology; Proteins; Recombinant Fusion Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Temperature; Transcription Factors; Ubiquitin-Protein Ligases; vacuoles; Vacuoles - metabolism; Vesicular Transport Proteins; Yeasts; GFP; APG; autophagy; autophagosome; membrane dynamics
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/20.21.5971

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Apg proteins coordinate the formation of autophagosomes. Several key reactions performed by these proteins have been described, but a comprehensive understanding of the overall network is still lacking. Based on Apg protein localization, we have identified a novel structure that functions in autophagosome formation. This pre‐autophagosomal structure, containing at least five Apg proteins, i.e. Apg1p, Apg2p, Apg5p, Aut7p/Apg8p and Apg16p, is localized in the vicinity of the vacuole. Analysis of apg mutants revealed that the formation of both a phosphatidylethanolamine‐conjugated Aut7p and an Apg12p–Apg5p conjugate is essential for the localization of Aut7p to the pre‐autophagosomal structure. Vps30p/Apg6p and Apg14p, components of an autophagy‐ specific phosphatidylinositol 3‐kinase complex, Apg9p and Apg16p are all required for the localization of Apg5p and Aut7p to the structure. The Apg1p protein kinase complex functions in the late stage of autophagosome formation. Here, we present the classification of Apg proteins into three groups that reflect each step of autophagosome formation.