Autophagosome formation in relation to the endoplasmic reticulum
- PDF / 1,211,455 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 38 Downloads / 228 Views
pen Access
REVIEW
Autophagosome formation in relation to the endoplasmic reticulum Yo‑hei Yamamoto and Takeshi Noda*
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 phosphatidylino‑ sitol synthase (PIS)/CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and choline/ethanolamine phos‑ photransferase 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 mem‑ brane 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: Autophagy, Autophagosome, Endoplasmic reticulum, ERdj8/DNAJC16, Atg2, VMP1, TMEM41b, ATG9, COPII, PIS, CDIPT Background Autophagy (specifically macroautophagy) is an intracellular degradation system that maintains cellular homeostasis and is associated with many pathophysiological phenomena, including cancer and neurodegenerative diseases [1, 2]. Autophagy involves membrane structures called autophagosomes, which envelop the substrates and subsequently fuse with the lysosomes, resulting in the degradation of the substrates [3]. In the last 30 years, the molecular mechanism of autophagosome formation has been progressively understood. Autophagosome formation is controlled by a group of proteins called Atg *Correspondence: [email protected]‑u.ac.jp Center for Frontier Oral Sciences, Graduate School of Dentistry, Osaka University Graduate School, 1‑8 Yamadaoka, Suita, Osaka 565‑0871, Japan
proteins, which are evolutionarily conserved in eukaryotes [4, 5]. There are two types of autophagy: non-selective and selective. Non-selective autophagy engulfs cytoplasmic solution non-selectively, which includes soluble proteins among others. The diameter of non-selective autophagosomes is thought to be relatively uniform (~ 1 μm). Selective autophagy engulfs diverse substrates of various sizes while large autophagosomes enwrap large autophagic substrates such as mitochondria and bacteria [6–9]. The size
Data Loading...
