In selective autophagy of the nucleus (hereafter nucleophagy), nucleus-derived double-membrane vesicles (NDVs) are formed, sequestered within autophagosomes, and delivered to lysosomes or vacuoles for degradation. In Saccharomyces cerevisiae, the nuclear envelope (NE) protein Atg39 acts as a nucleophagy receptor, which interacts with Atg8 to target NDVs to the forming autophagosomal membranes. In this study, we revealed that Atg39 is anchored to the outer nuclear membrane via its transmembrane domain and also associated with the inner nuclear membrane via membrane-binding amphipathic helices (APHs) in its perinuclear space region, thereby linking these membranes. We also revealed that autophagosome formation-coupled Atg39 crowding causes the NE to protrude toward the cytoplasm, and the tips of the protrusions are pinched off to generate NDVs. The APHs of Atg39 are crucial for Atg39 crowding in the NE and subsequent NE protrusion. These findings suggest that the nucleophagy receptor Atg39 plays pivotal roles in NE deformation during the generation of NDVs to be degraded by nucleophagy.
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7 February 2022
Article|
January 21 2022
Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus
Keisuke Mochida
,
Keisuke Mochida
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
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Toshifumi Otani,
Toshifumi Otani
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
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Yuto Katsumata,
Yuto Katsumata
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
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Hiromi Kirisako,
Hiromi Kirisako
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
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Chika Kakuta,
Chika Kakuta
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
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Tetsuya Kotani,
Tetsuya Kotani
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
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Hitoshi Nakatogawa
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
Correspondence to Hitoshi Nakatogawa: hnakatogawa@bio.titech.ac.jp
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Keisuke Mochida
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
Toshifumi Otani
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
Yuto Katsumata
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
Hiromi Kirisako
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
Chika Kakuta
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
Tetsuya Kotani
1
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
Correspondence to Hitoshi Nakatogawa: hnakatogawa@bio.titech.ac.jp
K. Mochida’s present address is Laboratory for Protein Conformation Diseases, RIKEN Center for Brain Science, Wako, Japan.
Received:
March 26 2021
Revision Received:
November 12 2021
Accepted:
December 10 2021
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
KAKENHI
- Award Id(s): JP17H01430,JP19H05708
Funder(s):
Ministry of Education, Culture, Sports, Science and Technology
Funder(s):
Japan Agency for Medical Research and Development
- Award Id(s): JP21gm1410004
Funder(s):
Tokyo Tech Fund
© 2022 Mochida et al.
2022
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2022) 221 (2): e202103178.
Article history
Received:
March 26 2021
Revision Received:
November 12 2021
Accepted:
December 10 2021
Citation
Keisuke Mochida, Toshifumi Otani, Yuto Katsumata, Hiromi Kirisako, Chika Kakuta, Tetsuya Kotani, Hitoshi Nakatogawa; Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus. J Cell Biol 7 February 2022; 221 (2): e202103178. doi: https://doi.org/10.1083/jcb.202103178
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