JUNQ and IPOD

JUNQ and IPOD are types of cytosolic protein inclusion bodies in eukaryotes.

Neurodegenerative diseases, such as Parkinson's, Alzheimer's, and Huntington's, are associated and correlated with protein aggregation and accumulation of misfolded proteins in inclusion bodies. For many years, protein aggregation was considered a random process by which misfolded proteins stick to each other to form inclusions^[1] (imagine a bundle of hairs haphazardly piling up in a corner of a room). Moreover, protein aggregates were thought to be toxic agents and the cause for neuronal dysfunction and death. However, recent studies, using advanced methods (i.e. fluorescence microscopy), show that protein aggregation may actually be a tightly regulated, organized process, by which the cell protects itself from toxic proteins by sequestration to inclusion bodies.^[2] In 2008, Daniel Kaganovich working in the Frydman lab showed that eukaryotic cells sort misfolded proteins into two distinct inclusion bodies in a well-managed cellular process:^[3]

1. The JUNQ (JUxta Nuclear Quality control compartment)
2. The IPOD (Insoluble Protein Deposit)

JUNQ and IPOD are evolutionarily conserved, and are found in specific and defined cellular sites. Delivery of misfolded, aggregated proteins to JUNQ and IPOD require an intact cytoskeleton and specific cellular quality control components, such as Heat Shock Proteins (HSPs).^[4] The partition into the two distinct inclusion bodies is due to the different handling and processing of different kinds of misfolded proteins (e.g. ubiquitinated vs. non-ubiquitinated proteins). Segregation of toxic protein aggregates into JUNQ and IPOD inclusion bodies is a means by which mammalian cells can be rejuvenated through asymmetric division.^[5]

Thus, the discovery of JUNQ and IPOD provided a new striking perspective of how cells manage misfolded aggregated proteins and gave convincing proof that protein aggregation is a non-random, well regulated and controlled cellular process. Furthermore, the discovery of JUNQ and IPOD suggested that in addition to temporal quality control (i.e. time dependent administration of damaged proteins) cells exploit homeostasis spatially:^[6] If degradation isn't available, protection of the cellular environment from a misfolded protein is accomplished by its sequestration to an aggregate inclusion.^{[citation needed]}