Heavy water causes yeast to build cell wall in overdrive

Water is essential for all living things to survive. But not any water will do. When its hydrogen atoms are substituted by deuterium—the naturally occurring hydrogen isotope with both a proton and a neutron in its nucleus rather than just a proton—this heavy water (D₂O) stunts the growth of most organisms. Researchers now report that fission yeast, Schizosaccharomyces pombe, grows poorly in D₂O because D₂O drives the one-celled organism to beef up its cell wall. Strains of S. pombe with mutations in the pathway responsible for this fortification grew in D₂O just fine, the researchers found (ACS Synth. Biol., 2020 DOI: 10.1021/acssynbio.9b00376). Such mutants unaffected by D₂O could be useful for producing deuterium-labeled proteins for research.

Rasmus Hartmann-Petersen, a biologist at the University of Copenhagen, and his colleagues started exploring how S. pombe grows in D₂O on a lark. Unlike bacteria, which can adapt to increasing D₂O concentrations, S. pombe cells cannot, the team found. S. pombe cells grown in D₂O don’t die–they just don’t multiply. Their cell walls grow, however–they get thicker.

“The cell wall is basically the skin of the cell, to protect it from the environment,” says Hartmann-Petersen. “If there is some sort of stress condition, then the cell will activate this pathway to make a more thick cell wall.”

In order to screen for genes that help S. pombe adapt to D₂O, Hartmann-Petersen and his colleagues then created mutant strains missing individual genes and looked for those that grew better in D₂O than in regular water. They identified four genes–all key components of a cellular signaling pathway that controls the integrity of the cell wall.

The clear identification of the cell integrity pathway is interesting, says Katerina Bisova, a microbiologist at the Czech Academy of Sciences. The study “unravels some specific genes making cells more resistant/sensitive to D₂O,” she says.

Researchers sometimes use D₂O to label proteins they are studying in order to follow track them as they go about their cellular business. Most often they produce them in the bacterium Escherichia coli, which adapts to D₂O well. But some proteins must be produced in eukaryotic cells, like yeast–so it may be possible to make them in S. pombe cells carrying these mutations, he says.