The relation between autophagy and the ubiquitin-proteasome system in toxicology

Introduction: Proteotoxicity refers to the detrimental effects of damaged/misfolded proteins on the cell. The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) are two major pathways responsible for degradation of most cellular proteins. Alterations of UPS and ALP functions are associated with the accumulation of proteotoxic species in the cells.. Emerging evidence suggests that proteasome inhibition or impairment activates autophagy and conversely, acute ALP inhibition may sometimes increase intrinsic proteasome peptidase activities but chronic ALP inhibition hinders UPS performance in ubiquitinated protein degradation. The exact molecular basis on which the two degradative pathways interact remains largely undefined.Method: Here we review current understanding of the roles of the UPS and autophagy in the control of cell toxicity with a specific focus on the crosstalk between the two pathways.