To save or degrade: balancing proteasome homeostasis to maximize cell survival

Autophagic degradation of proteasomes (termed proteaphagy) is a conserved mechanism by which cells eliminate excess or damaged particles. This clearance is induced rapidly when organisms are starved for nitrogen and, because proteasomes are highly abundant, their breakdown likely makes an important contribution to the amino acid pools necessary for survival. By contrast, our recent studies found that proteasomes are not degraded in response to carbon starvation, even though bulk macroautophagy is similarly activated. Instead, carbon starvation induces sequestration of proteasomes into membrane-less cytoplasmic condensates previously termed proteasome storage granules (PSGs), which protect proteasomes from autophagic degradation. Preserving proteasomes in PSGs enhances the ability of yeast cells to recover from a variety of stresses, implying that rapid remobilization of stored proteasomes when conditions improve is advantageous to cell fitness. Consequently, the choice of whether to save or degrade proteasomes can profoundly impact cell survival.