The nascent polypeptide-associated complex is a key regulator of proteostasis

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Cellular adaptation to stress relies on regulating protein synthesis.
• The nascent polypeptide-associated complex (NAC) is a ribosome-bound chaperone.
• Protein homeostasis (proteostasis) is vital for cell viability.

Purpose of the Study:

• To investigate the role of NAC in linking translation to the cellular protein-folding environment.
• To elucidate NAC's function as a proteostasis sensor under various stress conditions.

Main Methods:

• Observing NAC localization and ribosome association under non-stress and stress conditions.
• Analyzing the impact of NAC relocalization on translational capacity.
• Investigating NAC's response to aging, heat shock, and aggregation-prone proteins (polyglutamine, Aβ-peptide).

Main Results:

• NAC associates with ribosomes to promote translation and folding under normal conditions.
• During proteostasis imbalance, NAC relocates to protein aggregates, depleting its ribosome-bound pool.
• This depletion reduces translation and nascent protein flux, observed in aging, heat shock, and with aggregation-prone proteins.

Conclusions:

• NAC functions as a central proteostasis sensor, integrating the folding state of the proteome with cellular stress responses.
• NAC provides a feedback mechanism controlling translational activity based on cellular proteostasis.
• NAC's dynamic localization regulates protein synthesis adaptation to environmental and physiological challenges.