ERdj8 governs the size of autophagosomes during the formation process

Yo-Hei Yamamoto; Ayano Kasai; Hiroko Omori; Tomoe Takino; Munechika Sugihara; Tetsuo Umemoto; Maho Hamasaki; Tomohisa Hatta; Tohru Natsume; Richard I Morimoto; Ritsuko Arai; Satoshi Waguri; Miyuki Sato; Ken Sato; Shoshana Bar-Nun; Tamotsu Yoshimori; Takeshi Noda; Kazuhiro Nagata

doi:10.1083/jcb.201903127

ERdj8 governs the size of autophagosomes during the formation process

J Cell Biol. 2020 Aug 3;219(8):e201903127. doi: 10.1083/jcb.201903127.

Authors

Yo-Hei Yamamoto^{1

2

3}, Ayano Kasai⁴, Hiroko Omori⁵, Tomoe Takino⁴, Munechika Sugihara⁴, Tetsuo Umemoto⁶, Maho Hamasaki^{6

7}, Tomohisa Hatta^{8

9}, Tohru Natsume^{8

9}, Richard I Morimoto¹⁰, Ritsuko Arai¹¹, Satoshi Waguri¹¹, Miyuki Sato¹², Ken Sato^{13

14}, Shoshana Bar-Nun¹⁵, Tamotsu Yoshimori^{6

7}, Takeshi Noda^{1

16}, Kazuhiro Nagata^{2

3

4}

Affiliations

¹ Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka, Japan.
² Institute for Protein Dynamics, Kyoto Sangyo University, Kyoto, Japan.
³ Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology, Saitama, Japan.
⁴ Laboratory of Molecular and Cellular Biology, Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan.
⁵ Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
⁶ Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
⁷ Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁸ Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
⁹ Robotic Biology Institute, Inc., Tokyo, Japan.
¹⁰ Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL.
¹¹ Department of Anatomy and Histology, Fukushima Medical University School of Medicine, Fukushima, Japan.
¹² Laboratory of Molecular Membrane Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
¹³ Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
¹⁴ Gunma University Initiative for Advanced Research, Gunma, Japan.
¹⁵ Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
¹⁶ Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan.

Abstract

In macroautophagy, membrane structures called autophagosomes engulf substrates and deliver them for lysosomal degradation. Autophagosomes enwrap a variety of targets with diverse sizes, from portions of cytosol to larger organelles. However, the mechanism by which autophagosome size is controlled remains elusive. We characterized a novel ER membrane protein, ERdj8, in mammalian cells. ERdj8 localizes to a meshwork-like ER subdomain along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins. ERdj8 overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8 ablation resulted in a defect in engulfing larger targets. C. elegans, in which the ERdj8 orthologue dnj-8 was knocked down, could perform autophagy on smaller mitochondria derived from the paternal lineage but not the somatic mitochondria. Thus, ERdj8 may play a critical role in autophagosome formation by providing the capacity to target substrates of diverse sizes for degradation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Video-Audio Media

MeSH terms

Animals
Animals, Genetically Modified
Autophagosomes / genetics
Autophagosomes / metabolism*
Autophagosomes / ultrastructure
Autophagy-Related Proteins / genetics
Autophagy-Related Proteins / metabolism
CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / genetics
CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / metabolism
COS Cells
Caenorhabditis elegans / embryology
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Chlorocebus aethiops
Endoplasmic Reticulum / genetics
Endoplasmic Reticulum / metabolism*
Endoplasmic Reticulum / ultrastructure
HSP40 Heat-Shock Proteins / genetics
HSP40 Heat-Shock Proteins / metabolism*
HeLa Cells
Humans
Macroautophagy*
Mitochondria / metabolism
Mitochondria / ultrastructure

Substances

Autophagy-Related Proteins
Caenorhabditis elegans Proteins
DNAJC16 protein, human
HSP40 Heat-Shock Proteins
CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase

Abstract

Publication types

MeSH terms

Substances

Grants and funding