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

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The nuclear proteome contains many stress-sensitive proteins, necessitating robust quality control mechanisms.
• Protein conformational maintenance is crucial for cellular function, especially under stress conditions.

Purpose of the Study:

• To investigate the role of the nucleolus in nuclear protein quality control under stress.
• To elucidate the mechanisms by which the nucleolus manages misfolded proteins.

Main Methods:

• Utilized mammalian tissue culture cells subjected to stress.
• Observed the behavior of misfolded proteins within the nucleolus using microscopy.
• Assessed the involvement of nucleolar proteins (e.g., NPM1) and heat shock protein 70 (Hsp70) in protein management.

Main Results:

• Misfolded proteins accumulated in the granular component (GC) phase of the nucleolus under stress.
• Nucleolar proteins like NPM1 transiently bound misfolded proteins, reducing their mobility and preventing aggregation.
• Hsp70 mediated the refolding and removal of proteins from the nucleolus during stress recovery.
• Prolonged stress caused a transition of the nucleolar matrix from liquid-like to solid, leading to irreversible aggregation and quality control failure.

Conclusions:

• The nucleolus exhibits chaperone-like properties, aiding in nuclear protein maintenance during stress.
• The nucleolus serves as a dynamic storage site for misfolded proteins, with limited capacity.
• Nucleolar dysfunction under prolonged stress highlights the critical balance of protein quality control mechanisms.