Cell：日科学家发现细胞自噬奥秘
生物谷： 自噬作用是细胞加速新陈代谢，或者在饥饿时获得能量的一个重要手段，但是自噬作用是如何完成的，科学家一直不得而知。日本科学家最新报告说，一种小分子蛋白在自噬作用过程中必不可少。
据此间媒体１５日报道，自噬指细胞分解细胞质等自身构成成分的现象。自噬在各种生命活动中发挥着重要作用，比如它可以加速细胞内的新陈代谢，或者在细胞处于饥饿状态时从分解产物中获得能量。自噬过程中，细胞需要一个特殊的“口袋”将有待分解的物质包围并隔离起来，这个叫做自噬体的“口袋”由双层脂质膜构成，其形成机制一直是个谜。
日本科学技术振兴机构和基础生物学研究所的科学家们研究发现，一种名为“Ａｔｇ８”蛋白质在自噬体形成过程中功不可没。研究人员在实验中发现“Ａｔｇ８”和一种磷脂分子结合后，就可以黏合脂质膜，进而形成自噬体。
在使用酵母进行的实验中，如果彻底破坏“Ａｔｇ８”的功能，酵母细胞内就不能形成自噬体，而如果“Ａｔｇ８”的部分功能受损，酵母细胞形成的自噬体明显比正常细胞的自噬体小。相关论文刊登在最新一期美国《细胞》杂志网络版上。（新华网）
原始出处:
Cell, Vol 130, 165-178, 13 July 2007
Article
Atg8, a Ubiquitin-like Protein Required for Autophagosome Formation, Mediates Membrane Tethering and Hemifusion
Hitoshi Nakatogawa,1,2 Yoshinobu Ichimura,1,3 and Yoshinori Ohsumi1,
1 Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan
2 PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan
Corresponding author
Yoshinori Ohsumi
yohsumi@nibb.ac.jp
Autophagy involves de novo formation of double membrane-bound structures called autophagosomes, which engulf material to be degraded in lytic compartments. Atg8 is a ubiquitin-like 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.
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