The mammalian ULK1 complex and autophagy initiation.
The mammalian ULK1 complex and autophagy initiation.
复制标题
DOI：
10.1042/ebc20170021
复制
发表时间：
2017-12-12
影响因子：
6.4
通讯作者：
Ganley IG
中科院分区：
文献类型：
--
作者：
Zachari M;Ganley IG
自噬是一种重要的溶酶体降解途径，可作为质量控制机制。它去除细胞中受损的、有毒的或过量的细胞成分，如果让这些成分持续存在，可能会对细胞有害。它还作为一种循环途径，在饥饿条件下维持蛋白质合成。自噬中的一个关键初始事件是自噬体的形成，自噬体是一种独特的双膜细胞器，其吞噬注定要降解的细胞溶质货物。该步骤由丝氨酸/苏氨酸蛋白激酶ULK 1（unc-51样激酶1）介导，其在与至少三种蛋白质伴侣的复合物中起作用：FIP 200（200 kDa的粘着斑激酶家族相互作用蛋白）、ATG（自噬相关蛋白）13（ATG 13）和ATG 101。在这篇文章中，我们集中在自噬启动过程中ULK 1复合物的调节。上游通路的复杂模式汇聚在ULK 1上，表明该复合物作为一个节点，将多种信号转化为自噬体形成。在这里，我们回顾了我们目前对这种调节的理解，并反过来讨论了一旦ULK 1复合物被激活，下游会发生什么。
Autophagy is a vital lysosomal degradation pathway that serves as a quality control mechanism. It rids the cell of damaged, toxic or excess cellular components, which if left to persist could be detrimental to the cell. It also serves as a recycling pathway to maintain protein synthesis under starvation conditions. A key initial event in autophagy is formation of the autophagosome, a unique double-membrane organelle that engulfs the cytosolic cargo destined for degradation. This step is mediated by the serine/threonine protein kinase ULK1 (unc-51-like kinase 1), which functions in a complex with at least three protein partners: FIP200 (focal adhesion kinase family interacting protein of 200 kDa), ATG (autophagy-related protein) 13 (ATG13), and ATG101. In this artcile, we focus on the regulation of the ULK1 complex during autophagy initiation. The complex pattern of upstream pathways that converge on ULK1 suggests that this complex acts as a node, converting multiple signals into autophagosome formation. Here, we review our current understanding of this regulation and in turn discuss what happens downstream, once the ULK1 complex becomes activated.