Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Shinjyuku, Japan.
Antioxid Redox Signal. 2011 Jun;14(11):2201-14. doi: 10.1089/ars.2010.3482. Epub 2010 Dec 4.
Autophagy (macroautophagy), or the degradation of large numbers of cytoplasmic components, is induced by extracellular and intracellular signals, including oxidative stress, ceramide, and endoplasmic reticulum stress. This dynamic process involves membrane formation and fusion, including autophagosome formation, autophagosome-lysosome fusion, and the degradation of intra-autophagosomal contents by lysosomal hydrolases. Autophagy is associated with tumorigenesis, neurodegenerative diseases, cardiomyopathy, Crohn's disease, fatty liver, type II diabetes, defense against intracellular pathogens, antigen presentation, and longevity. Among the proteins and multimolecular complexes that contribute to autophagosome formation are the PI(3)-binding proteins, the PI3-phosphatases, the Rab proteins, the Atg1/ULK1 protein-kinase complex, the Atg9•Atg2-Atg18 complex, the Vps34-Atg6/beclin1 class III PI3-kinase complex, and the Atg12 and Atg8/LC3 conjugation systems. Two ubiquitin-like modifications, the Atg12 and LC3 conjugations, are essential for membrane elongation and autophagosome formation. Recent findings have revealed that processes of selective autophagy, including pexophagy, mitophagy, ERphagy (reticulophagy), and the p62-dependent degradation of ubiquitin-positive aggregates, are physiologically important in various disease states, whereas "classical" autophagy is considered nonselective degradation. Processes of selective autophagy require specific Atg proteins in addition to the "core" Atg complexes. Finally, methods to monitor autophagic activity in mammalian cells are described.
自噬（macroautophagy），或大量细胞质成分的降解，是由细胞外和细胞内信号诱导的，包括氧化应激、神经酰胺和内质网应激。这个动态过程涉及膜的形成和融合，包括自噬体的形成、自噬体-溶酶体融合以及溶酶体水解酶对内自噬体内容物的降解。自噬与肿瘤发生、神经退行性疾病、心肌病、克罗恩病、脂肪肝、II 型糖尿病、细胞内病原体的防御、抗原呈递和长寿有关。参与自噬体形成的蛋白质和多分子复合物包括 PI(3)结合蛋白、PI3 磷酸酶、Rab 蛋白、Atg1/ULK1 蛋白激酶复合物、Atg9·Atg2-Atg18 复合物、Vps34-Atg6/beclin1 类 III PI3-激酶复合物和 Atg12 和 Atg8/LC3 缀合系统。两种泛素样修饰，即 Atg12 和 LC3 缀合，对于膜伸长和自噬体形成是必不可少的。最近的发现表明，选择性自噬的过程，包括pexophagy、mitophagy、ERphagy（reticulophagy）和 p62 依赖性泛素阳性聚集体的降解，在各种疾病状态下具有生理重要性，而“经典”自噬被认为是非选择性降解。选择性自噬过程除了“核心”Atg 复合物之外，还需要特定的 Atg 蛋白。最后，描述了监测哺乳动物细胞自噬活性的方法。
