Eskelinen Eeva-Liisa
Division of Biochemistry, Department of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Int Rev Cell Mol Biol. 2008;266:207-47. doi: 10.1016/S1937-6448(07)66005-5.
Macroautophagy is a self-digesting pathway responsible for the removal of long-lived proteins and organelles by the lysosomal compartment. Parts of the cytoplasm are first segregated in double-membrane-bound autophagosomes, which then undergo a multistep maturation process including fusion with endosomes and lysosomes. The segregated cytoplasm is then degraded by the lysosomal hydrolases. The discovery of ATG genes has greatly enhanced our understanding of the mechanisms of this pathway. Two novel ubiquitin-like protein conjugation systems were shown to function during autophagosome formation. Autophagy has been shown to play a role in a wide variety of physiological processes including energy metabolism, organelle turnover, growth regulation, and aging. Impaired autophagy can lead to diseases such as cardiomyopathy and cancer. This review summarizes current knowledge about the formation and maturation of autophagosomes, the role of macroautophagy in various physiological and pathological conditions, and the signaling pathways that regulate this process in mammalian cells.
巨自噬是一种自我消化途径，负责通过溶酶体区室清除长寿蛋白和细胞器。部分细胞质首先被隔离在双膜包裹的自噬体中，然后自噬体经历包括与内体和溶酶体融合在内的多步成熟过程。随后，被隔离的细胞质被溶酶体水解酶降解。自噬相关基因（ATG基因）的发现极大地增进了我们对这一途径机制的理解。研究表明，两种新型泛素样蛋白偶联系统在自噬体形成过程中发挥作用。自噬已被证明在包括能量代谢、细胞器更新、生长调节和衰老在内的多种生理过程中发挥作用。自噬功能受损会导致诸如心肌病和癌症等疾病。本综述总结了目前关于自噬体形成和成熟的知识、巨自噬在各种生理和病理条件下的作用，以及在哺乳动物细胞中调节这一过程的信号通路。
