Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK.
Nat Cell Biol. 2010 Aug;12(8):747-57. doi: 10.1038/ncb2078. Epub 2010 Jul 18.
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 derive from pre-autophagosomal structures. The membrane origins of autophagosomes are unclear and may involve multiple sources, including the endoplasmic reticulum and mitochondria. Here we show in mammalian cells that the heavy chain of clathrin interacts with Atg16L1 and is involved in the formation of Atg16L1-positive early autophagosome precursors. Atg16L1 associated with clathrin-coated structures, and inhibition of clathrin-mediated internalization decreased the formation of both Atg16L1-positive precursors and mature autophagosomes. We tested and demonstrated that the plasma membrane contributes directly to the formation of early Atg16L1-positive autophagosome precursors. This may be particularly important during periods of increased autophagosome formation, because the plasma membrane may serve as a large membrane reservoir that allows cells periods of autophagosome synthesis at levels many-fold higher than under basal conditions, without compromising other processes.
自噬是一种溶酶体降解细胞内物质的过程，这些物质是通过双层膜自噬体运输的。自噬体由吞噬体的延伸和融合形成，吞噬体来源于前自噬体结构。自噬体的膜起源尚不清楚，可能涉及多个来源，包括内质网和线粒体。在这里，我们在哺乳动物细胞中表明，网格蛋白重链与 Atg16L1 相互作用，并参与形成 Atg16L1 阳性的早期自噬体前体。Atg16L1 与网格蛋白包被结构相关，网格蛋白介导的内吞作用抑制减少了 Atg16L1 阳性前体和成熟自噬体的形成。我们进行了测试并证明，质膜直接参与早期 Atg16L1 阳性自噬体前体的形成。在自噬体形成增加的时期，这可能特别重要，因为质膜可以作为一个大的膜储库，允许细胞在高于基础条件的水平上进行自噬体合成，而不会影响其他过程。
