Reversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly
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ABSTRACT: Cells respond to stress by blocking translation, rewiring metabolism, and forming transient mRNP assemblies called stress granules (SGs). After stress release, re-establishing homeostasis requires energy-consuming processes. However, the molecular mechanisms whereby cells restore energy production to disassemble SGs and reinitiate growth after stress remain poorly understood. Here we show that, upon stress, the ATP-producing enzyme Cdc19 forms inactive amyloids, and that their rapid re-solubilization is essential to restore energy production and SG disassembly. Cdc19 re-solubilization is initiated by the glycolytic metabolite fructose-1,6-bisphosphate (FBP), which directly binds Cdc19 amyloids and facilitates conformational changes that allow Hsp104 and Ssa2 chaperone recruitment. FBP then promotes Cdc19 tetramerization and activity, which together with trehalose breakdown boosts glycolysis to further enhance SG disassembly. Together, these results provide a molecular mechanism protecting cells during stress by directly coupling metabolism and ATP production with SG dynamics via regulation of Cdc19 amyloids.
INSTRUMENT(S): Q TRAP
ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)
SUBMITTER: Ilaria Piazza
LAB HEAD: Paola Picotti
PROVIDER: PXD026060 | Pride | 2021-08-17
REPOSITORIES: Pride
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