TY - JOUR TI - Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation AU - Petrovska, Ivana AU - Nüske, Elisabeth AU - Munder, Matthias C AU - Kulasegaran, Gayathrie AU - Malinovska, Liliana AU - Kroschwald, Sonja AU - Richter, Doris AU - Fahmy, Karim AU - Gibson, Kimberley AU - Verbavatz, Jean-Marc AU - Alberti, Simon A2 - Kelly, Jeffery W VL - 3 PY - 2014 DA - 2014/04/25 SP - e02409 C1 - eLife 2014;3:e02409 DO - 10.7554/eLife.02409 UR - https://doi.org/10.7554/eLife.02409 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 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. KW - metabolic enzyme KW - metabolism KW - intracellular pH KW - protein aggregation KW - macromolecular crowding KW - quiescence JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -