Geng Jiefei, Klionsky Daniel J
Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Michigan 48109-2216, USA.
EMBO Rep. 2008 Sep;9(9):859-64. doi: 10.1038/embor.2008.163.
As a lysosomal/vacuolar degradative pathway that is conserved in eukaryotic organisms, autophagy mediates the turnover of long-lived proteins and excess or aberrant organelles. The main characteristic of autophagy is the formation of a double-membrane vesicle, the autophagosome, which envelops part of the cytoplasm and delivers it to the lysosome/vacuole for breakdown and eventual recycling of the degradation products. Among the approximately 30 autophagy-related (Atg) genes identified so far, there are two ubiquitin-like proteins, Atg12 and Atg8. Analogous to ubiquitination, Atg12 is conjugated to Atg5 by Atg7--an E1-like protein--and Atg10--an E2-like protein. Similarly, Atg7 and Atg3 are the respective E1-like and E2-like proteins that mediate the conjugation of Atg8 to phosphatidylethanolamine. Both Atg12-Atg5 and Atg8 localize to the developing autophagosome. The Atg12-Atg5 conjugate facilitates the lipidation of Atg8 and directs its correct subcellular localization. Atg8-phosphatidylethanolamine is probably a scaffold protein that supports membrane expansion and the amount present correlates with the size of autophagosomes.
作为真核生物中保守的溶酶体/液泡降解途径，自噬介导长寿命蛋白质以及多余或异常细胞器的周转。自噬的主要特征是形成双膜囊泡即自噬体，它包裹部分细胞质并将其递送至溶酶体/液泡进行分解以及降解产物的最终循环利用。在目前已鉴定的约30个自噬相关（Atg）基因中，有两个类泛素蛋白，即Atg12和Atg8。与泛素化类似，Atg12通过类E1蛋白Atg7和类E2蛋白Atg10与Atg5结合。同样，Atg7和Atg3分别是介导Atg8与磷脂酰乙醇胺结合的类E1蛋白和类E2蛋白。Atg12-Atg5和Atg8均定位于正在形成的自噬体。Atg12-Atg5结合物促进Atg8的脂化并指导其正确的亚细胞定位。Atg8-磷脂酰乙醇胺可能是一种支架蛋白，支持膜扩张，其含量与自噬体大小相关。
