The nucleolus functions as a phase-separated protein quality control compartment

Phasing-in quality control in the nucleus The fundamental process of protein quality control in the nucleus is not well understood. The nucleus contains several non–membrane-bound subcompartments forming liquid-like condensates. The largest of these is the nucleolus, the site of ribosome biogenesis. Frottin et al. found that metastable nuclear proteins that misfold upon heat stress enter the nucleolus. In the nucleolus, they avoid irreversible aggregation and remain competent for heat shock protein 70–dependent refolding upon recovery from stress. Prolonged stress or the uptake of proteins associated with neurodegenerative diseases prevented this reversibility. Thus, the properties of a phase-separated compartment can assist in protein quality control. Science , this issue p. 342