Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 20Y, UK.
Cell. 2011 Jul 22;146(2):303-17. doi: 10.1016/j.cell.2011.06.023.
Autophagy is a catabolic process in which lysosomes degrade intracytoplasmic contents transported in double-membraned autophagosomes. Autophagosomes are formed by the elongation and fusion of phagophores, which can be derived from preautophagosomal structures coming from the plasma membrane and other sites like the endoplasmic reticulum and mitochondria. The mechanisms by which preautophagosomal structures elongate their membranes and mature toward fully formed autophagosomes still remain unknown. Here, we show that the maturation of the early Atg16L1 precursors requires homotypic fusion, which is essential for subsequent autophagosome formation. Atg16L1 precursor homotypic fusion depends on the SNARE protein VAMP7 together with partner SNAREs. Atg16L1 precursor homotypic fusion is a critical event in the early phases of autophagy that couples membrane acquisition and autophagosome biogenesis, as this step regulates the size of the vesicles, which in turn appears to influence their subsequent maturation into LC3-positive autophagosomes.
自噬是一种溶酶体降解细胞内物质的分解代谢过程，这些物质是通过双层膜自噬体运输的。自噬体由吞噬体的伸长和融合形成，吞噬体可以来源于来自质膜和内质网、线粒体等其他部位的前自噬体结构。前自噬体结构如何伸长其膜并向完全形成的自噬体成熟的机制仍不清楚。在这里，我们表明，早期 Atg16L1 前体的成熟需要同源融合，这对于随后的自噬体形成是必不可少的。Atg16L1 前体同源融合依赖于 SNARE 蛋白 VAMP7 以及伙伴 SNARE。Atg16L1 前体同源融合是自噬早期阶段的一个关键事件，它将膜的获得与自噬体的生物发生偶联在一起，因为这一步骤调节了囊泡的大小，而这反过来又似乎影响了它们随后成熟为 LC3 阳性自噬体。
