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Metabolic tuning enables immediate adaptation to energy stress in yeast

ABSTRACT: In Saccharomyces cerevisiae, glucose depletion induces metabolic reprogramming through widespread transcriptional and translational reorganization. We report that initial very rapid translational silencing is driven by a specialized metabolic mechanism. Following glucose withdrawal, intracellular NTP levels drop drastically over 30 sec, before stabilizing at a regulated, post-stress set-point. Programmed translational control results from the differential NTP affinities of key enzymes; ATP falls below the (high) binding constants for DEAD-box helicase initiation factors, including eIF4A, driving mRNA release and blocking 80S assembly. Contrastingly, GTP levels always greatly exceed the (low) binding constants for elongation factors, allowing ribosome run-off and orderly translation shutdown. Translation initiation is immediately lost on all pre-existing mRNAs, before being selectively re-established on newly synthesized, upregulated stress-response transcripts. This response is unique to, and potentially de-risks, rapid glycolytic growth. We conclude that enzymatic constants are tuned for metabolic remodeling, allowing hierarchical inhibition of energy-consuming processes on very rapid timescales.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE285035 | GEO | 2025/11/26

REPOSITORIES: GEO

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Rapid remodeling of NTP levels enables immediate translational adaptation to energy stress in yeast

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