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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Article numbere201903127
JournalJournal of Cell Biology
Volume219
Issue number8
DOIs
StatePublished - Aug 3 2020

Funding

We thank Dr. S. Yamaoka (Tokyo Medical and Dental University, Tokyo, Japan) for pMRX-IRES-puro vector; T. Kitamura (The University of Tokyo, Tokyo, Japan) for Plat-E cells; and R. Yamashita (Kyoto Sangyo University, Kyoto, Japan) for worm experiments. SpinSR10 at the Advanced Cell imaging Core, Osaka University, was utilized in this study. This work is supported by the Japanese Society for the Promotion of Science KAKENHI (16K07347 to T. Noda and 18H04002 to K. Nagata); a grant from the Takeda Science Foundation (to K. Nagata); the Japan Science and Technology Agency CREST (JPMJCR13M6 to K. Nagata); and the joint research program of the Institute for Molecular and Cellular Regulation, Gunma University (16026 to Y.-H. Yamamoto). The authors declare no competing financial interests. Author contributions: Conceptualization, Y.-H. Yamamoto, T. Noda., and K. Nagata; Writing ? Original Draft, Y.-H. Yamamoto, S. Bar-Nun, K. Nagata, and T. Noda. Writing ? Review and Editing, T. Noda. Investigation, Y.-H. Yamamoto (most aspects of the study); S. Bar-Nun (topology analysis); A. Kasai (mitophagy analysis). T. Takino, M. Sugihara, and M. Sato. (worm experiments); T. Umemoto (bead assays); T. Hatta (mass spec); H. Omori, R. Arai., S. Waguri, (EM analysis); resources, R.I. Morimoto, M. Hamasaki, T. Yoshimori, K. Sato, and T. Natsume. This work is supported by the Japanese Society for the Promotion of Science KAKENHI (16K07347 to T. Noda and 18H04002 to K. Nagata); a grant from the Takeda Science Foundation (to K. Nagata); the Japan Science and Technology Agency CREST (JPMJCR13M6 to K. Nagata); and the joint research program of the Institute for Molecular and Cellular Regulation, Gunma University (16026 to Y.-H. Yamamoto). The authors declare no competing financial interests.

ASJC Scopus subject areas

  • Cell Biology

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