Discovery of Atg5/Atg7-independent alternative macroautophagy
Discovery of Atg5/Atg7-independent alternative macroautophagy
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DOI：
10.1038/nature08455
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发表时间：
2009-10-01
期刊：
影响因子：
64.8
通讯作者：
Shimizu, Shigeomi
中科院分区：
文献类型：
--
作者：
Nishida, Yuya;Arakawa, Satoko;Shimizu, Shigeomi
巨噬是一种通过产生自噬体/自噬酶体导致亚细胞成分大量降解的过程（1-3）。Atg5（文献4）和Atg7（文献5）被认为是哺乳动物巨噬的必需基因。然而，本研究表明，缺乏Atg5或Atg7的小鼠细胞在受到某些应激源时仍然可以形成自噬体/自噬酶体并进行自噬介导的蛋白质降解。虽然微管相关蛋白轻链3 （LC3，也称为Map1lc3a）脂化形成LC3- ii通常被认为是巨噬的一个很好的指标(6)，但在巨噬的Atg5/ atg7非依赖性替代过程中并未发生这种情况。我们还发现这种可选的巨噬过程受几种自噬蛋白的调控，包括unc -51样激酶1 （Ulk1）和beclin 1。与传统的巨噬不同，自噬体似乎是通过分离膜与来自反式高尔基体和晚期内体的囊泡融合以依赖arab9的方式产生的。在体内，在几个胚胎组织中检测到不依赖atg5的选择性巨噬。在红细胞成熟过程中，它还具有清除线粒体的功能。这些结果表明，哺乳动物巨噬至少可以通过两种不同的途径发生：依赖Atg5/ atg7的常规途径和不依赖Atg5/ atg7的替代途径。
Macroautophagy is a process that leads to the bulk degradation of subcellular constituents by producing autophagosomes/autolysosomes(1-3). It is believed that Atg5 (ref. 4) and Atg7 (ref. 5) are essential genes for mammalian macroautophagy. Here we show, however, that mouse cells lacking Atg5 or Atg7 can still form autophagosomes/autolysosomes and perform autophagy-mediated protein degradation when subjected to certain stressors. Although lipidation of the microtubule-associated protein light chain 3 (LC3, also known as Map1lc3a) to form LC3-II is generally considered to be a good indicator of macroautophagy(6), it did not occur during the Atg5/Atg7-independent alternative process of macroautophagy. We also found that this alternative process of macroautophagy was regulated by several autophagic proteins, including Unc-51-like kinase 1 (Ulk1) and beclin 1. Unlike conventional macroautophagy, autophagosomes seemed to be generated in aRab9-dependent manner by the fusion of isolation membranes with vesicles derived from the trans-Golgi and late endosomes. In vivo, Atg5-independent alternative macroautophagy was detected in several embryonic tissues. It also had a function in clearing mitochondria during erythroid maturation. These results indicate that mammalian macroautophagy can occur through at least two different pathways: an Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.