Reggiori Fulvio
Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Curr Top Dev Biol. 2006;74:1-30. doi: 10.1016/S0070-2153(06)74001-7.
Autophagy is a degradative transport route conserved among all eukaryotic organisms. During starvation, cytoplasmic components are randomly sequestered into large double-membrane vesicles called autophagosomes and delivered into the lysosome/vacuole where they are destroyed. Cells are able to modulate autophagy in response to their needs, and under certain circumstances, cargoes, such as aberrant protein aggregates, organelles, and bacteria can be selectively and exclusively incorporated into autophagosomes. As a result, this pathway plays an active role in many physiological processes, and it is induced in numerous pathological situations because of its ability to rapidly eliminate unwanted structures. Despite the advances in understanding the functions of autophagy and the identification of several factors, named Atg proteins that mediate it, the mechanism that leads to autophagosome formation is still a mystery. A major challenge in unveiling this process arises from the fact that the origin and the transport mode of the lipids employed to compose these structures is unknown. This compendium will review and analyze the current data about the possible membrane source(s) with a particular emphasis on the yeast Saccharomyces cerevisiae, the leading model organism for the study of autophagosome biogenesis, and on mammalian cells. The information acquired investigating the pathogens that subvert autophagy in order to replicate in the host cells will also be discussed because it could provide important hints for solving this mystery.
自噬是所有真核生物中保守的一种降解性转运途径。在饥饿期间,细胞质成分被随机隔离到称为自噬体的大型双膜囊泡中,并被输送到溶酶体/液泡中进行降解。细胞能够根据自身需求调节自噬,在某些情况下,诸如异常蛋白质聚集体、细胞器和细菌等货物可以被选择性地且专门地纳入自噬体。因此,该途径在许多生理过程中发挥着积极作用,并且由于其能够快速清除不需要的结构,在众多病理情况下也会被诱导。尽管在理解自噬功能以及鉴定介导自噬的几种名为Atg蛋白的因子方面取得了进展,但导致自噬体形成的机制仍然是个谜。揭示这一过程的一个主要挑战源于用于构成这些结构的脂质的来源和运输方式尚不清楚这一事实。本综述将回顾和分析关于可能的膜来源的当前数据,特别强调酿酒酵母,这是研究自噬体生物发生的主要模式生物,以及哺乳动物细胞。还将讨论通过研究在宿主细胞中复制时破坏自噬的病原体所获得的信息,因为它可能为解开这个谜团提供重要线索。