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Two distinct mechanisms target the autophagy-related E3 complex to the pre-autophagosomal structure.


ABSTRACT: In autophagy, Atg proteins organize the pre-autophagosomal structure (PAS) to initiate autophagosome formation. Previous studies in yeast revealed that the autophagy-related E3 complex Atg12-Atg5-Atg16 is recruited to the PAS via Atg16 interaction with Atg21, which binds phosphatidylinositol 3-phosphate (PI3P) produced at the PAS, to stimulate conjugation of the ubiquitin-like protein Atg8 to phosphatidylethanolamine. Here, we discover a novel mechanism for the PAS targeting of Atg12-Atg5-Atg16, which is mediated by the interaction of Atg12 with the Atg1 kinase complex that serves as a scaffold for PAS organization. While autophagy is partially defective without one of these mechanisms, cells lacking both completely lose the PAS localization of Atg12-Atg5-Atg16 and show no autophagic activity. As with the PI3P-dependent mechanism, Atg12-Atg5-Atg16 recruited via the Atg12-dependent mechanism stimulates Atg8 lipidation, but also has the specific function of facilitating PAS scaffold assembly. Thus, this study significantly advances our understanding of the nucleation step in autophagosome formation.

SUBMITTER: Harada K 

PROVIDER: S-EPMC6405243 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Two distinct mechanisms target the autophagy-related E3 complex to the pre-autophagosomal structure.

Harada Kumi K   Kotani Tetsuya T   Kirisako Hiromi H   Sakoh-Nakatogawa Machiko M   Oikawa Yu Y   Kimura Yayoi Y   Hirano Hisashi H   Yamamoto Hayashi H   Ohsumi Yoshinori Y   Nakatogawa Hitoshi H  

eLife 20190227


In autophagy, Atg proteins organize the pre-autophagosomal structure (PAS) to initiate autophagosome formation. Previous studies in yeast revealed that the autophagy-related E3 complex Atg12-Atg5-Atg16 is recruited to the PAS via Atg16 interaction with Atg21, which binds phosphatidylinositol 3-phosphate (PI3P) produced at the PAS, to stimulate conjugation of the ubiquitin-like protein Atg8 to phosphatidylethanolamine. Here, we discover a novel mechanism for the PAS targeting of Atg12-Atg5-Atg16,  ...[more]

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