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

Nature cell biology 2021 Oct

filter terms:

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. © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

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. Reversible amyloids of pyruvate kinase couple cell metabolism and stress granule disassembly. Nature cell biology. 2021 Oct;23(10):1085-1094