Autophagosome formation in relation to the endoplasmic reticulum

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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 (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 proteins, which are evolutionarily conserved in eukaryotes.
The endoplasmic reticulum (ER) is an organelle that plays diverse roles, such as the synthesis of secreted proteins and membrane proteins [13], protein transport [14], misfolded protein degradation [15], lipid synthesis [16], and calcium storage [17].

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