Two distinct mechanisms target the autophagy-related E3 complex to the pre-autophagosomal structure
- Tokyo Institute of Technology, Japan
- Yokohama City University, Japan
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Hitoshi Nakatogawa
Funding
Ministry of Education, Culture, Sports, Science, and Technology (25111003)
- Hitoshi Nakatogawa
Ministry of Education, Culture, Sports, Science, and Technology (17H01430)
- Hitoshi Nakatogawa
Ministry of Education, Culture, Sports, Science, and Technology (23000015)
- Yoshinori Ohsumi
Japan Science and Technology Agency (JPMJCR13M7)
- Hitoshi Nakatogawa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Harada et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Two distinct mechanisms target the autophagy-related E3 complex to the pre-autophagosomal structure
eLife 8:e43088.
https://doi.org/10.7554/eLife.43088
