PT - JOURNAL ARTICLE AU - Ivana Petrovska AU - Elisabeth Nüske AU - Matthias C. Munder AU - Gayathrie Kulasegaran AU - Liliana Malinovska AU - Sonja Kroschwald AU - Doris Richter AU - Karim Fahmy AU - Kimberley Gibson AU - Jean-Marc Verbavatz AU - Simon Alberti TI - Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation AID - 10.1101/003277 DP - 2014 Jan 01 TA - bioRxiv PG - 003277 4099 - http://biorxiv.org/content/early/2014/04/11/003277.short 4100 - http://biorxiv.org/content/early/2014/04/11/003277.full AB - 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 enzyme 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.