Atg8 controls phagophore expansion during autophagosome formation
Atg8 controls phagophore expansion during autophagosome formation
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DOI：
10.1091/mbc.e07-12-1292
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发表时间：
2008-08-01
影响因子：
3.3
通讯作者：
Klionsky, Daniel J.
中科院分区：
文献类型：
--
作者：
Xie, Zhiping;Nair, Usha;Klionsky, Daniel J.
自噬是一种有效的细胞内降解过程，在健康和疾病中发挥着关键作用。Atg8是一种脂质结合的泛素样蛋白，是形成自噬体所必需的，自噬体是一种负责将细胞质物质传递到溶酶体的双膜囊泡。然而，Atg8如何以及何时在这一过程中发挥作用尚不清楚。在这里，我们表明，Atg8控制的自噬体前体，吞噬细胞的扩张，并给出了第一个实时的，基于观察的时间解剖的自噬体形成过程。我们证明了Atg8的量决定了自噬体的大小。在自噬体生物发生过程中，Atg 8形成一个扩展的结构，随后从囊泡形成的位点解离。在Atg 8动力学的基础上，我们提出了一个自噬体形成的多阶段模型。该模型为今后分析已知自噬相关蛋白的功能和动力学以及筛选新基因提供了基础。
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.