RT Journal Article
SR Electronic
T1 Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 003277
DO 10.1101/003277
A1 Ivana Petrovska
A1 Elisabeth Nüske
A1 Matthias C. Munder
A1 Gayathrie Kulasegaran
A1 Liliana Malinovska
A1 Sonja Kroschwald
A1 Doris Richter
A1 Karim Fahmy
A1 Kimberley Gibson
A1 Jean-Marc Verbavatz
A1 Simon Alberti
YR 2014
UL http://biorxiv.org/content/early/2014/04/11/003277.abstract
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.