Dynamics and diversity in autophagy mechanisms: lessons from yeast

Abstract

Eukaryotic cells have evolved a degradative pathway called autophagy that can deliver a large amount of cytoplasmic proteins and even whole organelles into lytic compartments, such as lysosomes in mammals or vacuoles in plant and yeast cells. Autophagy has vital roles in various physiological situations and is also involved in several pathological processes. A number of physiological signals and stresses can induce autophagy. Following its induction, double membrane-bound vesicles called autophagosomes are newly formed in the cytoplasm to sequester materials (cargoes) to be degraded. Two modes of cargo sequestration by autophagosomal membranes are suggested: non-selective (starvation-induced) autophagy, in which a portion of the cytoplasm is randomly engulfed, and selective autophagy, in which specific cargoes, such as toxic protein aggregates and superfluous or damaged organelles, are recognized and in many cases exclusively enwrapped by the membranes. Studies in yeast have identified a unique subset of proteins called autophagy-related (Atg) proteins, which contain core components that are commonly required for membrane formation in all types of autophagy. These components constitute several subgroups, such as a protein kinase complex, a lipid kinase complex and two ubiquitin-like conjugation systems. Atg proteins are concentrated at the site for membrane formation and organize a dynamic assembly called the preautophagosomal structure, in which Atg proteins specific for each type of autophagy (which differ in their induction signals and cargoes) are thought to serve as conductors that regulate the localization and activity of core machinery and determine the site and the mode of vesicle formation according to various situations.