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Reversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly

Item Type:Article
Title:Reversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly
Creators Name:Cereghetti, G., Wilson-Zbinden, C., Kissling, V.M., Diether, M., Arm, A., Yoo, H., Piazza, I., Saad, S., Picotti, P., Drummond, D.A., Sauer, U., Dechant, R. and Peter, M.
Abstract:Cells respond to stress by blocking translation, rewiring metabolism and forming transient messenger ribonucleoprotein assemblies called stress granules (SGs). After stress release, re-establishing homeostasis and disassembling SGs requires ATP-consuming processes. However, the molecular mechanisms whereby cells restore ATP production and disassemble SGs 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 ATP production and disassemble SGs in glucose-containing media. Cdc19 re-solubilization is initiated by the glycolytic metabolite fructose-1,6-bisphosphate, which directly binds Cdc19 amyloids, allowing Hsp104 and Ssa2 chaperone recruitment and aggregate re-solubilization. Fructose-1,6-bisphosphate then promotes Cdc19 tetramerization, which boosts its activity to further enhance ATP production and SG disassembly. Together, these results describe a molecular mechanism that is critical for stress recovery and directly couples cellular metabolism with SG dynamics via the regulation of reversible Cdc19 amyloids.
Keywords:Adenosine Triphosphate, Amyloid, Cell Cycle Proteins, Cytoplasmic Granules, Fructosediphosphates, HSP70 Heat-Shock Proteins, Heat-Shock Proteins, Physiological Stress, Pyruvate Kinase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:1085-1094
Date:October 2021
Additional Information:Erratum in: Nat Cell Biol (2021).
Official Publication:https://doi.org/10.1038/s41556-021-00760-4
PubMed:View item in PubMed

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