Proteasome-dependent degradation and nucleus-vacuole junctions sustain proteostasis during acute glucose starvation

How protein quality control is maintained during acute metabolic stress remains poorly understood. In budding yeast, abrupt glucose depletion rapidly lowers ATP levels and leads to the formation of chaperone-containing inclusions, suggesting that ATP-dependent degradation of misfolded proteins may be compromised when energy becomes limiting. Here we find that selective degradation of misfolded proteins remains active during acute glucose starvation despite reduced cellular ATP levels. Using model misfolded substrates in yeast Saccharomyces cerevisiae, we show that misfolded proteins continue to be efficiently degraded throughout both early and late phases of acute glucose depletion. This degradation requires the proteasome and depends on its functional 19S regulatory particle, indicating that ATP-dependent proteasomal activity persists during metabolic stress. We further find that nucleus-vacuole junctions (NVJs) promote efficient degradation during prolonged glucose starvation, revealing a role for organelle contact sites in supporting proteostasis under energy limitation. Together, these findings indicate that cells preserve proteasome-mediated proteostasis during acute glucose starvation, while NVJ membrane contact sites help sustain degradation capacity when metabolic resources are scarce.