Abstract
Protein aggregation is a continuous process in our cells. Some proteins aggregate in a regulated manner required for different vital functional processes in the cells whereas other protein aggregates result from misfolding caused by various stressors. The decision to form an aggregate is largely made by chaperones and chaperone-assisted proteins. Proteins that are damaged beyond repair are degraded either by the proteasome or by the lysosome via autophagy. The aggregates can be degraded by the proteasome and by chaperone-mediated autophagy only after dissolution into soluble single peptide species. Hence, protein aggregates as such are degraded by macroautophagy. The selective degradation of protein aggregates by macroautophagy is called aggrephagy. Here we review the processes of aggregate formation, recognition, transport, and sequestration into autophagosomes by autophagy receptors and the role of aggrephagy in different protein aggregation diseases.
Highlights
Misfolded proteins result from mutations, incomplete translation giving defective ribosomal products (DRiPs), misfolding after translation, aberrant protein modifications, oxidative damage, and from failed assembly of protein complexes
Proteins damaged beyond repair are recognized and sorted by chaperone and co-chaperone complexes containing chaperone-assisted ubiquitin E3 ligases to three different degradation pathways: the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and/or aggrephagy
A recent study explored the degradation of dendritic cell aggresome-like induced structures (DALISs) formed in dendritic cells, and this study revealed that the contents of DALIS can be degraded both by the proteasome and by selective autophagy [72]
Summary
Misfolded proteins result from mutations, incomplete translation giving defective ribosomal products (DRiPs), misfolding after translation, aberrant protein modifications, oxidative damage, and from failed assembly of protein complexes. The lysosomal degradation of intracellular contents, such as misfolded proteins, protein aggregates, and organelles, is mediated by autophagy [14, 15]. Macroautophagy (hereafter referred to as autophagy) is the only process that can mediate the degradation of larger substrates such as organelles, microbes, and protein aggregates (Figure 1). The assembly of autophagy substrates into larger aggregates or clustered structures is a common feature of selective autophagy [26] It may facilitate their uptake into autophagosomes, and aggregates may work as nucleation sites for the phagophore, the forming isolation membrane [40]. Proteins damaged beyond repair are recognized and sorted by chaperone and co-chaperone complexes containing chaperone-assisted ubiquitin E3 ligases to three different degradation pathways: the UPS, CMA, and/or aggrephagy. In the following we will review the current knowledge on how protein aggregates are recognized, sorted, and degraded by aggrephagy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
