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

Müller, Martin, Schmidt, Oliver, Angelova, Mihaela, Faserl, Klaus, Weys, Sabine, Kremser, Leopold, Pfaffenwimmer, Thaddäus, Dalik, Thomas, Kraft, Claudine, Trajanoski, Zlatko, Lindner, Herbert, Teis, David·2015·eLife

Abstract

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.

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Metadata

Authors
Müller, M., Schmidt, O., Angelova, M., Faserl, K., Weys, S., Kremser, L., Pfaffenwimmer, T., Dalik, T., Kraft, C., Trajanoski, Z., Lindner, H., & Teis, D.
Venue
eLife
Published
2015-04-22
Volume
4
ISSN
2050-084X
Cited by
117
References
15
Language
en
Funders
  • Human Frontier Science Program (HFSP) (CDA-00001/2010-C)
  • Austrian Science Fund (FWF) (Y444-B12, P 25522-B20, MCBO (W01101), SFB021 (F21))
  • European Molecular Biology Organization (EMBO) and Marie Curie Actions cofunding (ALTF 642-2012, EMBOCOFUND2010, GA-2010-267146)
  • MUI START (2013042023)
  • Tiroler Wissenschaftfonds
  • Vienna Science and Technology Fund (WWTF, VRG10-001)

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