Open AccessReversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly
Author(s) -
Gea Cereghetti,
Caroline Wilson-Zbinden,
Vera M. Kissling,
Maren Diether,
Alexandra Arm,
Haneul Yoo,
Ilaria Piazza,
Shady Saad,
Paola Picotti,
D. Allan Drummond,
Uwe Sauer,
Reinhard Dechant,
Matthias Peter
Publication year - 2021
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-021-00760-4
Subject(s) - stress granule , biochemistry , microbiology and biotechnology , glycolysis , metabolism , cellular stress response , kinase , chaperone (clinical) , biology , chemistry , translation (biology) , fight or flight response , messenger rna , medicine , pathology , gene
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.