Glucose Starvation Inhibits Autophagy via Vacuolar Hydrolysis and Induces Plasma Membrane Internalization by Down-regulating Recycling

• Published in: The Journal of biological chemistry Vol. 289; no. 24; pp. 16736 - 16747
• Main Authors: Lang, Michael J., Martinez-Marquez, Jorge Y., Prosser, Derek C., Ganser, Laura R., Buelto, Destiney, Wendland, Beverly, Duncan, Mara C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.06.2014; American Society for Biochemistry and Molecular Biology
• Subjects: Autophagy; Cell Biology; Cell Membrane - metabolism; Down-Regulation; Endocytosis; Endosome; Energy Metabolism; Glucose; Glucose - deficiency; Glucose - metabolism; Hydrolysis; Intracellular Trafficking; Lipid Metabolism; Lysosome; Mechanistic Target of Rapamycin Complex 1; Membrane Recycling; Multiprotein Complexes - metabolism; Protein Transport; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; TOR Serine-Threonine Kinases - metabolism; Vacuoles - metabolism; Membrane Recycling; Endocytosis; Energy Metabolism; Lysosome; Intracellular Trafficking; Glucose; Autophagy; Endosome
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.525782

Cellular energy influences all aspects of cellular function. Although cells can adapt to a gradual reduction in energy, acute energy depletion poses a unique challenge. Because acute depletion hampers the transport of new energy sources into the cell, the cell must use endogenous substrates to replenish energy after acute depletion. In the yeast Saccharomyces cerevisiae, glucose starvation causes an acute depletion of intracellular energy that recovers during continued glucose starvation. However, how the cell replenishes energy during the early phase of glucose starvation is unknown. In this study, we investigated the role of pathways that deliver proteins and lipids to the vacuole during glucose starvation. We report that in response to glucose starvation, plasma membrane proteins are directed to the vacuole through reduced recycling at the endosomes. Furthermore, we found that vacuolar hydrolysis inhibits macroautophagy in a target of rapamycin complex 1-dependent manner. Accordingly, we found that endocytosis and hydrolysis are required for survival in glucose starvation, whereas macroautophagy is dispensable. Together, these results suggest that hydrolysis of components delivered to the vacuole independent of autophagy is the cell survival mechanism used by S. cerevisiae in response to glucose starvation. Background: During energy starvation, cells utilize intracellular resources for survival; however, the resources used during glucose starvation are unknown. Results: In glucose-starved yeast, vacuolar hydrolysis and endocytosis promote survival whereas autophagy is dispensable. Conclusion: Vacuolar hydrolysis blocks autophagy and provides resources for survival during glucose starvation. Significance: This new survival mechanism could protect cells from starvation in many situations.