National Institute of Biological Sciences, Beijing, China.
Autophagy. 2011 Feb;7(2):159-65. doi: 10.4161/auto.7.2.14223. Epub 2011 Feb 1.
Macroautophagy (hereafter referred to as autophagy) involves the formation of a closed, double membrane structure, called the autophagosome. Most of the Atg proteins that are essential for autophagosome formation are evolutionarily conserved between yeast and higher eukaryotes. The functions of some Atg proteins, however, are mediated by highly divergent proteins in mammalian cells. In this study, we identified a novel coiled-coil domain protein, EPG-8, that plays an essential role in the autophagy pathway in C. elegans. Mutations in epg-8 cause defects in degradation of various autophagy substrates and also compromise survival of animals under nutrient-depletion conditions. In epg-8 mutants, lipidated LGG-1 (the C. elegans Atg8 homolog) accumulates but does not form distinct punctate structures. EPG-8 directly interacts with the C. elegans Beclin 1 homolog, BEC-1. Our study demonstrates that epg-8 may function as a highly divergent homolog of the yeast autophagy gene Atg14.
自噬（以下简称自噬）涉及形成一个封闭的双层膜结构，称为自噬体。对于自噬体形成至关重要的大多数 Atg 蛋白在酵母和高等真核生物之间是进化保守的。然而，一些 Atg 蛋白的功能是由哺乳动物细胞中高度分化的蛋白质介导的。在这项研究中，我们鉴定了一种新型卷曲螺旋结构域蛋白 EPG-8，它在秀丽隐杆线虫的自噬途径中发挥着重要作用。epg-8 突变导致各种自噬底物降解缺陷，并在营养缺乏条件下损害动物的存活。在 epg-8 突变体中，脂化的 LGG-1（秀丽隐杆线虫 Atg8 同源物）积累但不能形成明显的点状结构。EPG-8 直接与秀丽隐杆线虫 Beclin 1 同源物 BEC-1 相互作用。我们的研究表明，epg-8 可能作为酵母自噬基因 Atg14 的高度分化同源物发挥作用。
