Phagophore closure, autophagosome maturation and autophagosome fusion during macroautophagy in the yeast Saccharomyces cerevisiae

Abstract

Macroautophagy, hereafter referred to as autophagy, is a complex process in which multiple membrane‐remodeling events lead to the formation of a cisterna known as the phagophore, which then expands and closes into a double‐membrane vesicle termed the autophagosome. During the past decade, enormous progress has been made in understanding the molecular function of the autophagy‐related proteins and their role in generating these phagophores. In this Review, we discuss the current understanding of three membrane remodeling steps in autophagy that remain to be largely characterized; namely, the closure of phagophores, the maturation of the resulting autophagosomes into fusion‐competent vesicles, and their fusion with vacuoles/lysosomes. Our review will mainly focus on the yeast Saccharomyces cerevisiae, which has been the leading model system for the study of molecular events in autophagy and has led to the discovery of the major mechanistic concepts, which have been found to be mostly conserved in higher eukaryotes.

ATG8 delipidation is not universally critical for autophagy in plants

“…S7A, C and D ). Surprisingly, the size of autophagic bodies in the WT cells overexpressing the ATG8I isoform was significantly smaller under –N conditions when compared to the puncta size in the same transgenic line under –C or AZD treatment (0.51 μm 2 under –N vs 0.76 μm 2 under –C, or 0.69 μm 2 under AZD, Tukey’s HSD test p -value <0.001; Fig. S7A and D ), thereby explaining the observed stunted root growth on nitrogen-depleted medium.…”

“…Notably, autophagosome biogenesis in yeast cells occurs in proximity to the vacuole, at the single phagophore assembly site 2 ( Fig. 6 ).…”

“…ATG8 recruits other core ATG proteins to the growing phagophore. Subsequently, delipidation of ATG8 from maturing autophagosome was suggested to release PAS proteins prior to the fusion of the autophagosome with the lytic compartment thus preventing their unnecessary degradation 2 . Interestingly, such release of the core ATGs might be less critical for Arabidopsis autophagy.…”

“…Effective cargo sequestration relies on continuous extension of the autophagosomal membrane to create adequately sized vesicles. Subsequently, these autophago-somes must be sealed before fusing with the lytic compartment to avoid the leakage of hydrolases into the cytoplasm 2 .…”

Autophagy—from yeast to humans: Thirty years of molecular autophagy

“…Then, in 1993, the molecular era of autophagy research began with the isolation of S. cerevisiae mutants defective in autophagy, followed by the identification of the corresponding yeast ATG (autophagy related) genes [2,23,24]. The sophisticated molecular mechanisms of autophagosome biogenesis and their fusion with the vacuole with a focus on S. cerevisiae as a model organism are detailed in the graphical review by Shatz and Elazar [25], and the review by Kraft and Reggiori [26]. The elegant structural and functional relationship of the autophagic machinery is further dissected in the review by Noda [27].…”