Sanchez-Wandelmer Jana, Ktistakis Nicholas T, Reggiori Fulvio
Department of Cell Biology, Center for Molecular Medicine, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Signalling Programme, The Babraham Institute, Babraham, Cambridge CB22 3AT, UK
J Cell Sci. 2015 Jan 15;128(2):185-92. doi: 10.1242/jcs.158758.
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).
自噬体是自噬的标志，尽管它们在涉及囊泡运输至溶酶体或液泡的这种降解途径中发挥核心作用，但其生物发生的潜在机制仍在很大程度上未知。我们目前关于自噬体生物发生的概念基于一些模型，这些模型表明一个小的自主扁平囊通过其末端的扩张生长为自噬体。最近的研究发现，内质网（ER）出口位点（ERES），即蛋白质被分选进入分泌系统的特化内质网区域，是自噬体形成的关键参与者。由于新生自噬体与内质网的形态学联系，这引发了几个挑战我们当前对自噬体生物发生认知的问题，例如ERES是否是自噬体形成的区室？这种联系的功能相关性是什么？这些区室是为自噬体的产生提供必需分子和/或它们是这些囊泡出现的结构平台吗？在本假说中，我们讨论了最近将ERES与自噬体生物发生相关联的数据，并提出了两个模型来描述该区室在自噬体生物发生过程中不同步骤的可能作用。本文是关于自噬体生物发生焦点文章的一部分。如需进一步阅读，请参阅相关文章：Sven R. Carlsson和Anne Simonsen所著的“自噬体生物发生中的膜动力学”（《细胞科学杂志》128卷，193 - 205页）以及Tassula Proikas - Cezanne等人所著的“WIPI蛋白：新生自噬体上的必需磷脂酰肌醇3 - 磷酸效应器”（《细胞科学杂志》128卷，207 - 217页）。
