Autophagy in Yeast: Mechanistic Insights and Physiological Function

Abstract

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

Unraveling the complexity of flux regulation: A new method demonstrated for nutrient starvation in Saccharomyces cerevisiae

“…Among these enzymes, glucose-6-phosphate isomerase and ALD have a unique isoenzyme form, excluding that this apparent metabolic regulation is actually caused by K m changes through the expression of isoenzymes. During nitrogen starvation, unspecific degradation of proteins via autophagy is enhanced (12), and, therefore, one might have expected a proportional decrease of all enzyme amounts (corresponding to multisite modulation). We observed, however, disproportional changes in enzyme activities ( h s unequal to each other and 1).…”

Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons

“…Over time, damage to mitochondrial components from reactive oxygen species causes a decline in energy-producing capacity (Hagen et al, 1997) that triggers release from cytoskeletal anchoring, activation of dynein, and repression of kinesin-1. After retrograde transport to the cell body, senescent mitochondria are enclosed in membranes by autophagocytosis and then are degraded by fusion with lysosomes (Vargas et al, 1987;Abeliovich and Klionsky, 2001;RodriguezEnriquez et al, 2004). Regulatory mechanisms that control transitions between the three states may be triggered by extracellular signals, local ATP and ion concentrations, mitochondrial inner membrane potential, or other internal cues from mitochondria (Hollenbeck and Saxton, 2005).…”

Degradation of the Gluconeogenic Enzymes Fructose-1,6-bisphosphatase and Malate Dehydrogenase Is Mediated by Distinct Proteolytic Pathways and Signaling Events

“…Both Ypt7p and Vam3p have been shown to play important roles in many known trafficking pathways leading to the vacuole (53)(54)(55)(56)(57)(58)(59)(60). These include the sorting of carboxy peptidase Y to the vacuole (53), the targeting of autophagosomes to the vacuole, the cytosol to vacuole targeting pathway (54 -56), and homotypic vacuole fusion (57)(58)(59)(60).…”