The coordinated action of the MVB pathway and autophagy ensures cell survival during starvation

• Published in: eLife Vol. 4; p. e07736
• Main Authors: Müller, Martin, Schmidt, Oliver, Angelova, Mihaela, Faserl, Klaus, Weys, Sabine, Kremser, Leopold, Pfaffenwimmer, Thaddäus, Dalik, Thomas, Kraft, Claudine, Trajanoski, Zlatko, Lindner, Herbert, Teis, David
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 22.04.2015; eLife Sciences Publications, Ltd
• Subjects: Adaptation, Physiological; Amino acids; Autophagy; Autophagy - genetics; Biochemistry; Biodegradation; Cell Biology; Cell division; Cell survival; Cell Survival - genetics; Cytoplasm; Endocytosis; Gene Expression Regulation, Fungal; Gene Regulatory Networks; Homeostasis; Immunoglobulins; Lysosomal protein; Membrane proteins; Metabolic Networks and Pathways - genetics; Metabolism; Multivesicular Bodies - chemistry; Multivesicular Bodies - metabolism; MVB pathway; Phagocytosis; Plasma; Protein biosynthesis; Protein turnover; Proteins; Proteolysis; Proteomes; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Starvation; Starvation - genetics; Starvation - metabolism; Stress, Physiological; Vacuoles; Vacuoles - chemistry; Vacuoles - metabolism; MVB pathway; endocytosis; autophagy; cell biology; biochemistry; S. cerevisiae
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.07736

The degradation and recycling of cellular components is essential for cell growth and survival. Here we show how selective and non-selective lysosomal protein degradation pathways cooperate to ensure cell survival upon nutrient limitation. A quantitative analysis of starvation-induced proteome remodeling in yeast reveals comprehensive changes already in the first three hours. In this period, many different integral plasma membrane proteins undergo endocytosis and degradation in vacuoles via the multivesicular body (MVB) pathway. Their degradation becomes essential to maintain critical amino acids levels that uphold protein synthesis early during starvation. This promotes cellular adaptation, including the de novo synthesis of vacuolar hydrolases to boost the vacuolar catabolic activity. This order of events primes vacuoles for the efficient degradation of bulk cytoplasm via autophagy. Hence, a catabolic cascade including the coordinated action of the MVB pathway and autophagy is essential to enter quiescence to survive extended periods of nutrient limitation.