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Review
. 2020 Oct 22;27(1):97.
doi: 10.1186/s12929-020-00691-6.

Autophagosome formation in relation to the endoplasmic reticulum

Yo-Hei Yamamoto  1 , Takeshi Noda  2
Affiliations
Review

Autophagosome formation in relation to the endoplasmic reticulum

Yo-Hei Yamamoto et al. J Biomed Sci. .

Abstract

Autophagy is a process in which a myriad membrane structures called autophagosomes are formed de novo in a single cell, which deliver the engulfed substrates into lysosomes for degradation. The size of the autophagosomes is relatively uniform in non-selective autophagy and variable in selective autophagy. It has been recently established that autophagosome formation occurs near the endoplasmic reticulum (ER). In this review, we have discussed recent advances in the relationship between autophagosome formation and endoplasmic reticulum. Autophagosome formation occurs near the ER subdomain enriched with phospholipid synthesizing enzymes like phosphatidylinositol synthase (PIS)/CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and choline/ethanolamine phosphotransferase 1 (CEPT1). Autophagy-related protein 2 (Atg2), which is involved in autophagosome formation has a lipid transfer capacity and is proposed to directly transfer the lipid molecules from the ER to form autophagosomes. Vacuole membrane protein 1 (VMP1) and transmembrane protein 41b (TMEM41b) are ER membrane proteins that are associated with the formation of the subdomain. Recently, we have reported that an uncharacterized ER membrane protein possessing the DNAJ domain, called ERdj8/DNAJC16, is associated with the regulation of the size of autophagosomes. The localization of ERdj8/DNAJC16 partially overlaps with the PIS-enriched ER subdomain, thereby implying its association with autophagosome size determination.

Keywords: ATG9; Atg2; Autophagosome; Autophagy; CDIPT; COPII; ERdj8/DNAJC16; Endoplasmic reticulum; PIS; TMEM41b; VMP1.

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Conflict of interest statement

There are no competing interests to declare.

Figures

Fig. 1
Fig. 1
Schematic representation of the endoplasmic reticulum (ER) and the ER subdomain. The ER network is composed of tubules and sheet-like structures that are formed by the ER-shaping proteins, of which reticulon (red) creates the curvature of the ER membrane. CLIMP-63 (orange), which is a single spanning ER membrane protein, forms an oligomer into the ER luminal space to maintain the ER sheet structure. Atlastin (blue) localizes on the three-way junction of the ER network to create an interconnection of the ER tubules. The inset region shows the ER tubular matrices within the ER sheet structures. DFCP1 (green) localizes and forms the omegasome structures on the ER subdomain
Fig. 2
Fig. 2
ERdj8 localizes at the ER subdomain. Cos7 cells expressing RFP-Sec61β were stained with anti-Erdj8 and imaged by super-resolution microscopy (SpinSR10, OLYMPUS). Scale bar is 10 μm. ERdj8 forms the ER meshwork structures near the Sec61β weak signal and creates the ER subdomain
Fig. 3
Fig. 3
The expression level of ERdj8 alters the size of the autophagosomes. a Autophagosomes can capture both small and large substrates when ERdj8 expression is at the endogenous level. b ERdj8 overexpression induces the expansion of autophagosome membrane and both small and large substrates are degraded by autophagy. c Knockdown of ERdj8 induces the small autophagosomes to capture small substrates, whereas the degradation of large substrates is disabled
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