Work

Global proteolysis during starvation governs proteome remodeling and a survival–regrowth trade-off in bacteria

Year: 2026

Type: article

Abstract: , carbon starvation triggers large-scale proteome remodeling, with global proteolysis supplying both the amino acids (AAs) and ATP for protein synthesis. This remodeling occurs in two phases, with a short preparatory phase relying on constitutive proteolytic machinery and fueled by residual carbon waste, and a more extended phase, relying on starvation-induced protein components synthesized during the preparatory phase and fueled by AA catabolism. The starvation-induced protein degradation (SPD) program dominating the extended phase depends on YeaG, a little-known, broadly conserved protein highly expressed in stationary phase under the control of the general stress sigma factor RpoS. SPD fuels the synthesis of stress proteins, including those in the RpoS regulon and AA catabolic enzymes, markedly enhancing survival and accounting for much of the viability benefit conferred by RpoS during carbon starvation. However, in mutants where an energy source can be supplemented without enabling biomass growth, SPD and the accompanying protein synthesis are largely dispensable for survival, indicating that a primary physiological function of the synthesized stress proteins is to conserve or recycle energy during carbon starvation. Because SPD targets biosynthetic enzymes nonspecifically, proteome remodeling via SPD imposes a fundamental trade-off between long-term survival and short-term metabolic activity, manifested as a lag before regrowth upon nutrient replenishment. Together, these findings establish SPD as a general physiological strategy shaping protein synthesis and survival in nongrowing bacteria.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2611560123