Every protein begins as a chain of amino acids that must be folded, assembled, transported, and maintained correctly before it can perform its cellular function. When any part of that process goes wrong, damaged or misfolded proteins can accumulate, disrupting cellular activity and threatening cell survival. To protect themselves, cells rely on an interconnected network of quality-control systems that continually monitors the health of the proteome.

Molecular Biology of the Cell (MBoC) ASCB’s flagship journal, is highlighting advances in this essential area through its Protein Quality Control collection. The collection brings together research exploring how cells guide protein synthesis and folding, recognize defective proteins, activate stress responses, and remove proteins that cannot be repaired.

These mechanisms are fundamental to cellular physiology across organisms and cell types. They are also particularly relevant to conditions such as cancer and neurodegenerative disease, in which failures in protein homeostasis can contribute to protein aggregation, chronic cellular stress, and cell death.

Recent highlights from the Protein Quality Control collection include:

• Anthracyclines attenuate Nrf1-dependent proteolytic pathways and potentiate proteasome inhibitor cytotoxicity
• The kinesin Kar3 is required for endoplasmic reticulum–associated degradation
• TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in Saccharomyces cerevisiae
• Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance
• Differential reliance of CTD-nuclear envelope phosphatase 1 on its regulatory subunit in ER lipid synthesis and storage
• Mapping stress-responsive signaling pathways induced by mitochondrial proteostasis perturbations
• Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum function
• Cytoplasmic redox imbalance in the thioredoxin system activates Hsf1 and results in hyperaccumulation of the sequestrase Hsp42 with misfolded proteins
• The p24-family and COPII subunit SEC24C facilitate the clearance of alpha1-antitrypsin Z from the endoplasmic reticulum to lysosomes
• Small-molecule correctors divert CFTR-F508del from ERAD by stabilizing sequential folding states

Together, these studies demonstrate the many strategies cells use to preserve protein homeostasis. Research featured in the collection spans protein synthesis, folding and targeting; molecular chaperones; protein turnover and degradation; ER-associated degradation and ER stress; the heat shock, unfolded protein, and integrated stress responses; autophagy; protein aggregation; and the ubiquitin-proteasome system.

The Protein Quality Control special issue is led by Elizabeth Miller of the MRC Laboratory of Molecular Biology and Guillaume Thibault of Nanyang Technological University. Submissions are accepted on a rolling basis, allowing researchers to contribute new findings across the broad range of pathways that monitor, maintain, and restore proteome health.

Explore the Protein Quality Control collection and learn how you can contribute your own research to this important and rapidly advancing area of cell biology.

This post was collaboratively written by several ASCB staff members.