Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation

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Abstract

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.

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Ivana Petrovska

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Elisabeth Nüske

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Matthias C Munder

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Gayathrie Kulasegaran

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Liliana Malinovska

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Sonja Kroschwald

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Doris Richter

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Karim Fahmy

Helmholtz Institute Dresden-Rossendorf, Dresden, Germany

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The authors declare that no competing interests exist.
Kimberley Gibson

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Jean-Marc Verbavatz

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

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The authors declare that no competing interests exist.
Simon Alberti

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

For correspondence
alberti@mpi-cbg.de

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The authors declare that no competing interests exist.

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