Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion
Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion
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DOI：
10.1016/j.cell.2007.05.021
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发表时间：
2007-07-13
期刊：
影响因子：
64.5
通讯作者：
Ohsumi, Yoshinori
中科院分区：
文献类型：
--
作者：
Nakatogawa, Hitoshi;Ichimura, Yoshinobu;Ohsumi, Yoshinori
自噬涉及到被称为自噬小体的双层膜结合结构的从头形成，这些自噬小体吞噬在裂解的隔室中降解的物质。在酿酒酵母中，ATG8是这一过程所必需的泛素样蛋白，它可以通过泛素样系统与脂质磷脂酰乙醇胺偶联。在这里，我们使用一个体外系统，Atg8介导膜的拴系和半融合，这是由蛋白质的脂肪作用引起的，并由去结合酶Atg4可逆地调节。突变分析表明，体外观察到的膜系留和半融合代表了Atg8在体内自噬小体形成中的真实功能。此外，电子显微镜分析表明，Atg8的这些功能参与了自噬体膜的扩张。我们的结果进一步揭示了自噬独特的膜动力学机制，也表明了泛素样蛋白的功能多样性。
Autophagy involves de novo formation of double membrane- bound structures called autophagosomes, which engulf material to be degraded in lytic compartments. Atg8 is a ubiquitinlike protein required for this process in Saccharomyces cerevisiae that can be conjugated to the lipid phosphatidylethanolamine by a ubiquitin- like system. Here, we show using an in vitro system that Atg8 mediates the tethering and hemifusion of membranes, which are evoked by the lipidation of the protein and reversibly modulated by the deconjugation enzyme Atg4. Mutational analyses suggest that membrane tethering and hemifusion observed in vitro represent an authentic function of Atg8 in autophagosome formation in vivo. In addition, electron microscopic analyses indicate that these functions of Atg8 are involved in the expansion of autophagosomal membranes. Our results provide further insights into the mechanisms underlying the unique membrane dynamics of autophagy and also indicate the functional versatility of ubiquitin- like proteins.