Author:
Kishi-Itakura Chieko,Koyama-Honda Ikuko,Itakura Eisuke,Mizushima Noboru
Abstract
Autophagy is mediated by a unique organelle, the autophagosome. Autophagosome formation involves a number of autophagy-related (ATG) proteins and complicated membrane dynamics. Although the hierarchical relationships of ATG proteins have been investigated, how individual ATG proteins or their complexes contribute to the organization of the autophagic membrane remains largely unknown. Here, systematic ultrastructural analysis of mouse embryonic fibroblasts and HeLa cells deficient in various ATG proteins revealed that the emergence of the isolation membrane (phagophore) requires FIP200/RB1CC1, ATG9A, and PtdIns 3-kinase activity. By contrast, small premature isolation membrane- and autophagosome-like structures were generated in cells lacking VMP1 and ATG2A/B, respectively. The isolation membranes could elongate in cells lacking ATG5, but these did not mature into autophagosomes. We also found that ferritin clusters accumulated at the autophagosome formation site together with p62/SQSTM1 in autophagy-deficient cells. These results reveal the specific functions of these representative ATG proteins in autophagic membrane organization and ATG-independent recruitment of ferritin to the autophagosome formation site.
Publisher
The Company of Biologists
Cited by
192 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献