Xie Zhiping, Nair Usha, Klionsky Daniel J
Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Mol Biol Cell. 2008 Aug;19(8):3290-8. doi: 10.1091/mbc.e07-12-1292. Epub 2008 May 28.
Autophagy is a potent intracellular degradation process with pivotal roles in health and disease. Atg8, a lipid-conjugated ubiquitin-like protein, is required for the formation of autophagosomes, double-membrane vesicles responsible for the delivery of cytoplasmic material to lysosomes. How and when Atg8 functions in this process, however, is not clear. Here we show that Atg8 controls the expansion of the autophagosome precursor, the phagophore, and give the first real-time, observation-based temporal dissection of the autophagosome formation process. We demonstrate that the amount of Atg8 determines the size of autophagosomes. During autophagosome biogenesis, Atg8 forms an expanding structure and later dissociates from the site of vesicle formation. On the basis of the dynamics of Atg8, we present a multistage model of autophagosome formation. This model provides a foundation for future analyses of the functions and dynamics of known autophagy-related proteins and for screening new genes.
自噬是一种强大的细胞内降解过程，在健康和疾病中起着关键作用。Atg8是一种脂质结合的泛素样蛋白，是自噬体形成所必需的，自噬体是负责将细胞质物质输送到溶酶体的双膜囊泡。然而，Atg8在这个过程中如何以及何时发挥作用尚不清楚。在这里，我们表明Atg8控制自噬体前体——吞噬泡的扩张，并首次基于观察对自噬体形成过程进行了实时的时间解析。我们证明Atg8的量决定了自噬体的大小。在自噬体生物发生过程中，Atg8形成一个不断扩展的结构，随后从囊泡形成部位解离。基于Atg8的动态变化，我们提出了一个自噬体形成的多阶段模型。该模型为未来分析已知自噬相关蛋白的功能和动态变化以及筛选新基因提供了基础。
