title: ERES: sites for autophagosome biogenesis and maturation?
abstract: Autophagosomes are the hallmark of autophagy, but despite their central role in this degradative pathway that involves vesicle transport to lysosomes or vacuoles, the mechanism underlying their biogenesis still remains largely unknown. Our current concepts about autophagosome biogenesis are based on models suggesting that a small autonomous cisterna grows into an autophagosome through expansion at its extremities. Recent findings have revealed that endoplasmic reticulum (ER) exit sites (ERES), specialized ER regions where proteins are sorted into the secretory system, are key players in the formation of autophagosomes. Owing to the morphological connection of nascent autophagosomes with the ER, this has raised several questions that challenge our current perception of autophagosome biogenesis, such as are ERES the compartments where autophagosome formation takes place? What is the functional relevance of this connection? Are these compartments providing essential molecules for the generation of autophagosomes and/or are they structural platforms where these vesicles emerge? In this Hypothesis, we discuss recent data that have implicated the ERES in autophagosome biogenesis and we propose two models to describe the possible role of this compartment at different steps in the process of autophagosome biogenesis. This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: 'Membrane dynamics in autophagosome biogenesis' by Sven R. Carlsson and Anne Simonsen (J. Cell Sci. 128, 193-205) and 'WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome' by Tassula Proikas-Cezanne et al. (J. Cell Sci. 128, 207-217).
authors.affiliation: Department of Cell Biology, Center for Molecular Medicine, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Jana
authors.initials: J
authors.lastname: Sanchez-Wandelmer
authors.affiliation: Signalling Programme, The Babraham Institute, Babraham, Cambridge CB22 3AT, UK nicholas.ktistakis@babraham.ac.uk F.Reggiori@umcutrecht.nl.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ktistakis
authors.affiliation: Department of Cell Biology, Center for Molecular Medicine, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands nicholas.ktistakis@babraham.ac.uk F.Reggiori@umcutrecht.nl.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
mesh_terms: D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002450:Cell Communication / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C574794:ATG9A protein, human; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D033921:Vesicular Transport Proteins; C055525:phosphatidylinositol 3-phosphate
keywords: Autophagosome; Autophagy; Endoplasmic reticulum exit site; Isolation membrane; Phagophore; Phagophore assembly site; Pre-autophagosomal membrane