Abeliovich H, Klionsky D J
Department of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N. University Ave., Ann Arbor, MI 48109, USA.
Microbiol Mol Biol Rev. 2001 Sep;65(3):463-79, table of contents. doi: 10.1128/MMBR.65.3.463-479.2001.
Unicellular eukaryotic organisms must be capable of rapid adaptation to changing environments. While such changes do not normally occur in the tissues of multicellular organisms, developmental and pathological changes in the environment of cells often require adaptation mechanisms not dissimilar from those found in simpler cells. Autophagy is a catabolic membrane-trafficking phenomenon that occurs in response to dramatic changes in the nutrients available to yeast cells, for example during starvation or after challenge with rapamycin, a macrolide antibiotic whose effects mimic starvation. Autophagy also occurs in animal cells that are serum starved or challenged with specific hormonal stimuli. In macroautophagy, the form of autophagy commonly observed, cytoplasmic material is sequestered in double-membrane vesicles called autophagosomes and is then delivered to a lytic compartment such as the yeast vacuole or mammalian lysosome. In this fashion, autophagy allows the degradation and recycling of a wide spectrum of biological macromolecules. While autophagy is induced only under specific conditions, salient mechanistic aspects of autophagy are functional in a constitutive fashion. In Saccharomyces cerevisiae, induction of autophagy subverts a constitutive membrane-trafficking mechanism called the cytoplasm-to-vacuole targeting pathway from a specific mode, in which it carries the resident vacuolar hydrolase, aminopeptidase I, to a nonspecific bulk mode in which significant amounts of cytoplasmic material are also sequestered and recycled in the vacuole. The general aim of this review is to focus on insights gained into the mechanism of autophagy in yeast and also to review our understanding of the physiological significance of autophagy in both yeast and higher organisms.
单细胞真核生物必须能够快速适应不断变化的环境。虽然这种变化通常不会发生在多细胞生物的组织中，但细胞环境中的发育和病理变化往往需要与简单细胞中发现的适应机制并无二致的机制。自噬是一种分解代谢的膜运输现象，它会在酵母细胞可利用的营养物质发生剧烈变化时出现，例如在饥饿期间或用雷帕霉素（一种大环内酯类抗生素，其作用模拟饥饿）刺激后。自噬也发生在血清饥饿或受到特定激素刺激的动物细胞中。在巨自噬（自噬最常见的形式）中，细胞质物质被隔离在称为自噬体的双膜囊泡中，然后被运送到一个溶酶区室，如酵母液泡或哺乳动物溶酶体。通过这种方式，自噬允许对广泛的生物大分子进行降解和循环利用。虽然自噬仅在特定条件下被诱导，但自噬的显著机制方面以组成型方式发挥作用。在酿酒酵母中，自噬的诱导会使一种称为细胞质到液泡靶向途径的组成型膜运输机制从一种特定模式转变，在该特定模式中它携带驻留液泡水解酶氨基肽酶I，转变为一种非特异性的大量模式，在这种模式下大量细胞质物质也会被隔离并在液泡中循环利用。本综述的总体目标是关注对酵母自噬机制的深入了解，同时回顾我们对酵母和高等生物中自噬生理意义的理解。
