Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Cell Res. 2014 Jan;24(1):24-41. doi: 10.1038/cr.2013.168. Epub 2013 Dec 24.
Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.
自噬是一种主要的降解途径，发生在所有真核细胞中。它用于在应激条件下回收细胞质以产生大分子构建块和能量，去除多余和受损的细胞器以适应不断变化的营养条件，并维持细胞内稳态。此外，自噬通过防止有毒蛋白质的积累以及通过其在包括清除入侵微生物及其参与抗原呈递在内的免疫各个方面的作用，在细胞保护中发挥关键作用。最常见的自噬形式是巨自噬，在此过程中，细胞形成一个双膜隔离隔室，称为吞噬体，它成熟为自噬体。自噬体被递送至液泡或溶酶体后， cargo 被降解，产生的大分子被释放回细胞质中以供再利用。在过去的二十年中，酵母和其他真核生物中进行的自噬分子研究取得了巨大进展。人们对这个话题的兴趣增加的部分原因是自噬与包括癌症、肌肉疾病、糖尿病和神经退行性疾病在内的广泛人类病理生理学有关。然而，自噬仍有许多方面尚不清楚，包括吞噬体形成的过程、控制其诱导的调节机制以及大多数自噬相关蛋白的功能。在这篇综述中，我们重点介绍巨自噬，简要描述了这一过程在哺乳动物细胞中的发现，讨论了形成吞噬体的供体膜的当前观点，并描述了自噬机制，包括现有的结构信息。
