Protein quality control machinery: regulators of condensate architecture and functionality

Anitha Rajendran, Carlos A. Castañeda

Research output: Contribution to journalReview articlepeer-review

Abstract

Protein quality control (PQC) mechanisms including the ubiquitin (Ub)-proteasome system (UPS), autophagy, and chaperone-mediated refolding are essential to maintain protein homeostasis in cells. Recent studies show that these PQC mechanisms are further modulated by biomolecular condensates that sequester PQC components and compartmentalize reactions. Accumulating evidence points towards the PQC machinery playing a pivotal role in regulating the assembly, disassembly, and viscoelastic properties of several condensates. Here, we discuss how the PQC machinery can form their own condensates and also be recruited to known condensates under physiological or stress-induced conditions. We present molecular insights into how the multivalent architecture of polyUb chains, Ub-binding adaptor proteins, and other PQC machinery contribute to condensate assembly, leading to the regulation of downstream PQC outcomes and therapeutic potential.

Original languageEnglish (US)
Pages (from-to)106-120
Number of pages15
JournalTrends in Biochemical Sciences
Volume50
Issue number2
DOIs
StatePublished - Feb 2025

Keywords

  • chaperones
  • condensates
  • phase separation
  • polyphasic linkage
  • protein quality control
  • ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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