Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems

The ubiquitin proteasome system (UPS) and macroautophagy (hereafter called autophagy) were, for a long time, regarded as independent degradative pathways with few or no points of interaction. This view started to change recently, in the light of findings that have suggested that ubiquitylation can target substrates for degradation via both pathways. Moreover, perturbations in the flux through either pathway have been reported to affect the activity of the other system, and a number of mechanisms have been proposed to rationalise the link between the UPS and autophagy. Here we critically review these findings and outline some outstanding issues that still await clarification.