Protein synthesis upon acute nutrient restriction relies on proteasome function.

The mechanisms that protect mammalian cells against amino acid deprivation are only partially understood. We found that during an acute decrease in external amino acid supply, before up-regulation of the autophagosomal-lysosomal pathway, efficient translation was ensured by proteasomal protein degradation. Amino acids for the synthesis of new proteins were supplied by the degradation of preexisting proteins, whereas nascent and newly formed polypeptides remained largely protected from proteolysis. Proteasome inhibition during nutrient deprivation caused rapid amino acid depletion and marked impairment of translation. Thus, the proteasome plays a crucial role in cell survival after acute disruption of amino acid supply.