He Congcong, Klionsky Daniel J
Life Sciences Institute, Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
Autophagy. 2007 May-Jun;3(3):271-4. doi: 10.4161/auto.3912. Epub 2007 May 29.
The origin of the autophagosomal membrane and the lipid delivery mechanism during autophagy remain unsolved mysteries. Some important hints to these questions come from Atg9, which is the only integral membrane protein required for autophagosome formation and considered a membrane carrier in autophagy-related pathways. In S. cerevisiae, Atg9 cycles between peripheral sites and the pre-autophagosomal structure/phagophore assembly site (PAS), the nucleating site for formation of the sequestering vesicle. We recently identified a peripheral membrane protein, Atg11, as a binding partner of Atg9, in a yeast two-hybrid screen. Based on our analysis we propose a model for Atg9 cycling. Our model suggests that a pool of Atg11 mediates the anterograde transport of Atg9 to the PAS along the actin cytoskeleton, and that this delivery process may serve as a membrane shuttle for vesicle assembly during yeast selective autophagy. Here, we discuss the implications of the model and present additional evidence that extends it with regard to membrane trafficking modes during pexophagy.
自噬体膜的起源以及自噬过程中的脂质传递机制仍是未解之谜。关于这些问题的一些重要线索来自Atg9，它是自噬体形成所需的唯一整合膜蛋白，被认为是自噬相关途径中的膜载体。在酿酒酵母中，Atg9在外周位点和自噬前体结构/吞噬泡组装位点（PAS）之间循环，PAS是隔离囊泡形成的成核位点。我们最近在酵母双杂交筛选中鉴定出一种外周膜蛋白Atg11作为Atg9的结合伴侣。基于我们的分析，我们提出了一个Atg9循环的模型。我们的模型表明，一部分Atg11介导Atg9沿着肌动蛋白细胞骨架向PAS的顺向转运，并且这种传递过程可能在酵母选择性自噬期间作为囊泡组装的膜穿梭机制。在此，我们讨论该模型的意义，并提供额外证据，这些证据在过氧化物酶体自噬过程中的膜运输模式方面对该模型进行了扩展。
