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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...

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Autores principales: Petrovska, Ivana, Nüske, Elisabeth, Munder, Matthias C, Kulasegaran, Gayathrie, Malinovska, Liliana, Kroschwald, Sonja, Richter, Doris, Fahmy, Karim, Gibson, Kimberley, Verbavatz, Jean-Marc, Alberti, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
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
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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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