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

MPS-Authors
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Petrovska,  Ivana
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219498

Nüske,  Elisabeth
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219472

Munder,  Matthias
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219355

Kulasegaran,  Gayathrie
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219418

Malinovska,  Liliana
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219348

Kroschwald,  Sonja
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219580

Richter,  Doris
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219186

Gibson,  Kimberley
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219760

Verbavatz,  Jean-Marc
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons218962

Alberti,  Simon
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Petrovska, I., Nüske, E., Munder, M., Kulasegaran, G., Malinovska, L., Kroschwald, S., et al. (2014). Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation. eLife, 3: doi: 10.1101/003277.


Cite as: https://hdl.handle.net/21.11116/0000-0001-0576-5
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.