The role of ubiquitin in autophagy-dependent protein aggregate processing
The efficient management of misfolded protein aggregates is essential for cell viability and requires 3 interconnected pathways: the molecular chaperone machinery that assists protein folding, the proteasome pathway that degrades misfolded proteins, and the aggresomal pathway that sequesters and delivers toxic protein aggregates to autophagy for clearance. Although autophagy is generally considered as nonselective degradative machinery, growing evidence supports the existence of a selective autophagy that specifically targets protein aggregates for clearance. This "quality control autophagy" is established by specific ubiquitin E3 ligases, autophagic substrate ubiquitination, and specific ubiquitin-binding proteins p62 and HDAC6. In this context, quality control autophagy is similar to the proteasome system and utilizes ubiquitin tags for substrate recognition and processing. Here, I will discuss the recent progress toward understanding the molecular basis of this unique form of ubiquitin-dependent autophagy in protein aggregate clearance and its relevance to disease. © The Author(s) 2010.
