The ubiquitin-proteasome and macroautophagy-lysosome pathways are major routes for intracytosolic protein degradation. In many systems, proteasome inhibition is toxic. A Nature article by Pandey et al. shows that this toxicity can be modulated by altering autophagic activity. Their tantalizing results suggest that overexpression of HDAC6 may increase flux through the autophagy pathway, thereby attenuating the toxicity resulting from proteasome inhibition.