The role of metabolic priming in the translational response to glucose withdrawal

In Saccharomyces cerevisiae, glucose withdrawal produces a remarkably rapid and broad shutdown of protein production that is unique among stress responses.

Bresson et al (2020) recently demonstrated that arrest of translation, the final step in protein synthesis, occurs cell-wide within 30 seconds of glucose withdrawal.

Achieving this must require extensive signal amplification to allow external glucose depletion to generate an internal response involving thousands of effectors. However, a mechanistic understanding of how this occurs within seconds is currently lacking.

We hypothesise that a metabolic signalling mechanism facilitates the rapid translational response to glucose withdrawal and is dependent on the cellular metabolic state prior to this stress.

To investigate this, we aim to characterise the metabolic and translational response to glucose withdrawal by combining quantitative biochemical techniques with metabolomic technologies.

Such analyses will be conducted in S.cerevisiae strains with different metabolic backgrounds, assessing whether pre-stress metabolism affects the speed or extent of response.

The yeast S.cerevisiae is an established model organism for eukaryotic cells, so insights obtained should help understand responses of human cells to glucose depleted environments.

This is particularly relevant to treatment of cancer and inflammatory-mediated conditions, where altered cellular metabolism is implicated in disease development.