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

  1. Ivana Petrovska
  2. Elisabeth Nüske
  3. Matthias C Munder
  4. Gayathrie Kulasegaran
  5. Liliana Malinovska
  6. Sonja Kroschwald
  7. Doris Richter
  8. Karim Fahmy
  9. Kimberley Gibson
  10. Jean-Marc Verbavatz
  11. Simon Alberti  Is a corresponding author
  1. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  2. Helmholtz Institute Dresden-Rossendorf, Germany

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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Author details

  1. Ivana Petrovska

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Elisabeth Nüske

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthias C Munder

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Gayathrie Kulasegaran

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Liliana Malinovska

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Sonja Kroschwald

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Doris Richter

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Karim Fahmy

    Helmholtz Institute Dresden-Rossendorf, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Kimberley Gibson

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Jean-Marc Verbavatz

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Simon Alberti

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    alberti@mpi-cbg.de
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2014, Petrovska et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ivana Petrovska
  2. Elisabeth Nüske
  3. Matthias C Munder
  4. Gayathrie Kulasegaran
  5. Liliana Malinovska
  6. Sonja Kroschwald
  7. Doris Richter
  8. Karim Fahmy
  9. Kimberley Gibson
  10. Jean-Marc Verbavatz
  11. Simon Alberti
(2014)
Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation
eLife 3:e02409.
https://doi.org/10.7554/eLife.02409

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https://doi.org/10.7554/eLife.02409

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