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Comments on Yamamoto YH et al. (2020) J Cell Biol "ERdj8 governs the size of autophagosomes during the formation process." (0)
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Yamamoto YH, Kasai A, Omori H, Takino T, Sugihara M, Umemoto T, Hamasaki M, Hatta T, Natsume T, Morimoto RI, Arai R, Waguri S, Sato M, Sato K, Bar-Nun S, Yoshimori T, Noda T, & Nagata K (2020). ERdj8 governs the size of autophagosomes during the formation process. J Cell Biol, 219. doi:10.1083/jcb.201903127
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.
Authors: Yamamoto YH, Kasai A, Omori H, Takino T, Sugihara M, Umemoto T, Hamasaki M, Hatta T, Natsume T, Morimoto RI, Arai R, Waguri S, Sato M, Sato K, Bar-Nun S, Yoshimori T, Noda T, Nagata K