Cells use protein localization to control energy metabolism

Understanding how organisms adapt to changes in the availably of energy sources in their environment is important for understanding fundamental aspects of energy metabolism. In a recent study, published in the scientific journal Microbial Cell, researchers at Chalmers University of Technology have studied how yeast cells respond to changes in glucose concentration in their environment. The group of researchers, lead by Dr. Maria Cvjiovic and with contribution from Fluicell Technical Product Development Lead Dr. Niek Welkenhuysen, use single-cell approaches to demonstrate the important role that subcellular localization of protein kinases play in the cellular response to environmental changes and that only studying protein activation and inactivation alone is not sufficient for understanding how cells regulate their energy metabolism.

In their study, the researchers specifically investigated protein kinases in the Snf1/AMPK family, a highly conserved class of protein that regulates energy homeostasis in eukaryotic cells, including mammals, plants and fungi. In the yeast Saccharomyces cerevisiae, one of the roles of Snf1 is to direct the cell’s metabolism towards other carbon sources when hexose sugars such as glucose are unavailable.

There are multiple ways in which Snf1 regulates glucose metabolism and one, according to the authors, less well studied is the role the Snf1 localization plays in glucose repression. To determine the link between carbon source availability and Snf1 localization, the researchers measured the amount Snf1 present in the nucleus for cells grown with and without access to glucose. Their results showed that the relative nuclear localization is linked to the type of carbon source with little impact from changes in glucose concentration, indicating that the localization effect is sensitive to even low levels of glucose.

To study the cells’ response to changes in the environment, the researchers then used BioPen to rapidly change the carbon source environment around the cells from ethanol to either glucose, fructose or mannose. The carbon source upshift from ethanol to hexose sugars resulted in a dephosphorylation of Snf1, with the effect being most pronounced for glucose. The dephosphorylation of Snf1 was also correlated with and increase in the nuclear localization of Mig1, a regulatory protein that mediates the repression of genes required for the utilization of alternative carbon sources, signaling a metabolic shift to glucose and other fermentable sugars.

We are very happy that Dr. Cvjiovic and coworkers have chosen to use BioPen in their research and we look forward to obtaining further insights into cell metabolism from them in the future.

The article Exploring carbon source related localization and phosphorylation in the Snf1/Mig1 network using population and single cell-based approaches is available through Microbial Cell: https://microbialcell.com/researcharticles/2024a-braam-microbial-cell/

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