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

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
Article numbere201903127
JournalJournal of Cell Biology
Volume219
Issue number8
DOIs
StatePublished - 3 Aug 2020

Funding

FundersFunder number
Institute for Molecular and Cellular Regulation
Japanese Society for the Promotion of Science
Kyoto Sangyo University
National Institute on AgingP01AG054407
Takeda Science Foundation
Japan Society for the Promotion of Science16K07347, 18H04002
Japan Science and Technology AgencyJPMJCR13M6
Gunma University16026

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