Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
J Cell Biol. 2010 Jan 11;188(1):101-14. doi: 10.1083/jcb.200904075.
Macroautophagy is a catabolic pathway used for the turnover of long-lived proteins and organelles in eukaryotic cells. The morphological hallmark of this process is the formation of double-membrane autophagosomes that sequester cytoplasm. Autophagosome formation is the most complex part of macroautophagy, and it is a dynamic event that likely involves vesicle fusion to expand the initial sequestering membrane, the phagophore; however, essentially nothing is known about this process including the molecular components involved in vesicle tethering and fusion. In this study, we provide evidence that the subunits of the conserved oligomeric Golgi (COG) complex are required for double-membrane cytoplasm to vacuole targeting vesicle and autophagosome formation. COG subunits localized to the phagophore assembly site and interacted with Atg (autophagy related) proteins. In addition, mutations in the COG genes resulted in the mislocalization of Atg8 and Atg9, which are critical components involved in autophagosome formation.
自噬是一种用于真核细胞中长寿命蛋白质和细胞器周转的分解代谢途径。这个过程的形态学标志是双层膜自噬体的形成,它隔离细胞质。自噬体的形成是自噬的最复杂的部分,是一个动态的事件,可能涉及囊泡融合以扩大初始隔离膜——吞噬体;然而,这个过程的本质还几乎一无所知,包括参与囊泡锚定和融合的分子成分。在这项研究中,我们提供的证据表明,保守的寡聚高尔基体(COG)复合物的亚基是双层细胞质到液泡靶向囊泡和自噬体形成所必需的。COG 亚基定位于吞噬体组装位点,并与 Atg(自噬相关)蛋白相互作用。此外,COG 基因突变导致 Atg8 和 Atg9 的定位错误,而 Atg8 和 Atg9 是参与自噬体形成的关键成分。