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Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation
One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) form...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011332/ https://www.ncbi.nlm.nih.gov/pubmed/24771766 http://dx.doi.org/10.7554/eLife.02409 |
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author | Petrovska, Ivana Nüske, Elisabeth Munder, Matthias C Kulasegaran, Gayathrie Malinovska, Liliana Kroschwald, Sonja Richter, Doris Fahmy, Karim Gibson, Kimberley Verbavatz, Jean-Marc Alberti, Simon |
author_facet | Petrovska, Ivana Nüske, Elisabeth Munder, Matthias C Kulasegaran, Gayathrie Malinovska, Liliana Kroschwald, Sonja Richter, Doris Fahmy, Karim Gibson, Kimberley Verbavatz, Jean-Marc Alberti, Simon |
author_sort | Petrovska, Ivana |
collection | PubMed |
description | One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) forms filaments at low pH and that filament formation leads to enzymatic inactivation. Filament formation by Gln1 is a highly cooperative process, strongly dependent on macromolecular crowding, and involves back-to-back stacking of cylindrical homo-decamers into filaments that associate laterally to form higher order fibrils. Other metabolic enzymes also assemble into filaments at low pH. Hence, we propose that filament formation is a general mechanism to inactivate and store key metabolic enzymes during a state of advanced cellular starvation. These findings have broad implications for understanding the interplay between nutritional stress, the metabolism and the physical organization of a cell. DOI: http://dx.doi.org/10.7554/eLife.02409.001 |
format | Online Article Text |
id | pubmed-4011332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-40113322014-05-22 Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation Petrovska, Ivana Nüske, Elisabeth Munder, Matthias C Kulasegaran, Gayathrie Malinovska, Liliana Kroschwald, Sonja Richter, Doris Fahmy, Karim Gibson, Kimberley Verbavatz, Jean-Marc Alberti, Simon eLife Biochemistry One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) forms filaments at low pH and that filament formation leads to enzymatic inactivation. Filament formation by Gln1 is a highly cooperative process, strongly dependent on macromolecular crowding, and involves back-to-back stacking of cylindrical homo-decamers into filaments that associate laterally to form higher order fibrils. Other metabolic enzymes also assemble into filaments at low pH. Hence, we propose that filament formation is a general mechanism to inactivate and store key metabolic enzymes during a state of advanced cellular starvation. These findings have broad implications for understanding the interplay between nutritional stress, the metabolism and the physical organization of a cell. DOI: http://dx.doi.org/10.7554/eLife.02409.001 eLife Sciences Publications, Ltd 2014-04-25 /pmc/articles/PMC4011332/ /pubmed/24771766 http://dx.doi.org/10.7554/eLife.02409 Text en Copyright © 2014, Petrovska et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry Petrovska, Ivana Nüske, Elisabeth Munder, Matthias C Kulasegaran, Gayathrie Malinovska, Liliana Kroschwald, Sonja Richter, Doris Fahmy, Karim Gibson, Kimberley Verbavatz, Jean-Marc Alberti, Simon Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation |
title | Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation |
title_full | Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation |
title_fullStr | Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation |
title_full_unstemmed | Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation |
title_short | Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation |
title_sort | filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011332/ https://www.ncbi.nlm.nih.gov/pubmed/24771766 http://dx.doi.org/10.7554/eLife.02409 |
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