Figure 5

Potential mechanisms by which constituents of the UPS and chaperone proteins may affect development of PSI-induced inclusions in PC12 cells after proteasome inhibition by PSI. A, relevance of chaperone proteins in cytoplasm, ER and mitochondria resources to cytoplasmic constituents of the UPS establishes multiple routes of the UPS to remove aberrant and potentially cytotoxic proteins [2, 87]. The interaction between constituents of the UPS and cytoplasmic chaperon proteins might present one route to protein degradation in cytoplasm, UPP by which its target proteins serving as protein substrates of enzyme in the cytoplasm are directed by chaperone proteins to proteasomes [2]. The coordination between constituents of the UPS and ER chaperone proteins might present another route to protein degradation in ER, ERAD by which its target proteins serving as protein substrates of enzyme in lumen of the ER are bound to chaperone proteins, retro-translocated through a multi-protein translocon complex across ER membrane, get ubiquitinated by ubiquitin ligases, and are subsequently targeted for degradation by proteasomes [87]. New data support the notion that a route of the UPS similar to that observed in ERAD occurs in mitochondria and therefore the name of MAD has been proposed [87]. B, constituents of the UPS in cytoplasm and chaperone proteins in cytoplasm, ER and mitochondria resources, together with the protein substrates of the UPS, could be recruited to PSI-induced inclusions formed in PC12 cells after proteasome inhibition by PSI.