Sorting Out the JUNQ: The Spatial Nature of Protein Quality Control
Cambridge University Press
Microscopy and Microanalysis
Original Item ID
A healthy proteome is essential for survival, and cells have elaborate protein quality control (PQC) systems to maintain protein homeostasis, or proteostasis [1,2]. PQC systems are comprised of molecular chaperones which identify and bind misfolded proteins then target them for clearance by proteolytic pathways such as the proteasome or autophagy . Increasingly, defects in PQC are linked to human diseases such as Alzheimer’s, Parkinson’s, cancer and even aging [1-2]. One commonality among many of these diseases is the presence of intra- and extra-cellular inclusions containing misfolded proteins, which may result from a breakdown in PQC mechanisms leading to terminal sequestration of misfolded, toxic proteins. This demonstrates a critical need to better understand the complex PQC machinery as well as the mechanisms of inclusion formation and clearance. Misfolded proteins are actively sequestered into a number of distinct PQC compartments that are conserved from yeast to mammals . The juxtanuclear quality-control compartment (JUNQ), which forms when the proteasome is impaired, contains soluble misfolded proteins that can be refolded or cleared . A recent study proposed that the JUNQ actually resides inside the nucleus and should be renamed to INQ .
Sontag, Emily M.; Chen, Jian-Hua; McDermott, Gerry; Gestaut, Dan; Larabell, Carolyn; and Frydman, Judith, "Sorting Out the JUNQ: The Spatial Nature of Protein Quality Control" (2017). Biological Sciences Faculty Research and Publications. 906.