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

Autor/innen

  • G. Cereghetti
  • C. Wilson-Zbinden
  • V.M. Kissling
  • M. Diether
  • A. Arm
  • H. Yoo
  • I. Piazza
  • S. Saad
  • P. Picotti
  • D.A. Drummond
  • U. Sauer
  • R. Dechant
  • M. Peter

Journal

  • Nature Cell Biology

Quellenangabe

  • Nat Cell Biol 23 (10): 1085-1094

Zusammenfassung

  • 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.


DOI

doi:10.1038/s41556-021-00760-4