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首页> 外文期刊>Molecular biology of the cell >The Atg8 Conjugation System Is Indispensable for Proper Development of Autophagic Isolation Membranes in Mice
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The Atg8 Conjugation System Is Indispensable for Proper Development of Autophagic Isolation Membranes in Mice

机译：Atg8缀合系统对于小鼠自噬隔离膜的正确发育必不可少

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Autophagy is an evolutionarily conserved bulk-protein degradation pathway in which isolation membranes engulf the cytoplasmic constituents, and the resulting autophagosomes transport them to lysosomes. Two ubiquitin-like conjugation systems, termed Atg12 and Atg8 systems, are essential for autophagosomal formation. In addition to the pathophysiological roles of autophagy in mammals, recent mouse genetic studies have shown that the Atg8 system is predominantly under the control of the Atg12 system. To clarify the roles of the Atg8 system in mammalian autophagosome formation, we generated mice deficient in Atg3 gene encoding specific E2 enzyme for Atg8. Atg3-deficient mice were born but died within 1 d after birth. Conjugate formation of mammalian Atg8 homologues was completely defective in the mutant mice. Intriguingly, Atg12-Atg5 conjugation was markedly decreased in Atg3-deficient mice, and its dissociation from isolation membranes was significantly delayed. Furthermore, loss of Atg3 was associated with defective process of autophagosome formation, including the elongation and complete closure of the isolation membranes, resulting in malformation of the autophagosomes. The results indicate the essential role of the Atg8 system in the proper development of autophagic isolation membranes in mice.
机译：自噬是进化上保守的大蛋白降解途径，其中分离膜吞噬了细胞质成分，产生的自噬体将其转运至溶酶体。两个类似泛素的偶联系统，称为Atg12和Atg8系统，对于自噬体形成至关重要。除了自噬在哺乳动物中的病理生理作用外，最近的小鼠遗传研究表明Atg8系统主要受Atg12系统的控制。为了阐明Atg8系统在哺乳动物自噬体形成中的作用，我们生成了缺乏Atg3基因的小鼠，该基因编码Atg8的特异性E2酶。 Atg3缺陷小鼠已出生，但在出生后1天内死亡。在突变小鼠中，哺乳动物Atg8同源物的缀合物形成是完全有缺陷的。有趣的是，在Atg3缺陷型小鼠中，Atg12-Atg5的结合显着降低，并且其与分离膜的分离显着延迟。此外，Atg3的丧失与自噬小体形成的缺陷过程有关，包括分离膜的伸长和完全封闭，导致自噬小体畸形。结果表明Atg8系统在小鼠自噬隔离膜的正常发育中的重要作用。

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