Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water

Abstract

Life is completely dependent on water. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D₂O) and investigated the biological effects by a wide range of techniques, using Schizosaccharomyces pombe as model organism. We show that high concentrations of D₂O lead to altered glucose metabolism and growth retardation. After prolonged incubation in D₂O, cells displayed gross morphological changes, thickened cell walls, and aberrant cytoskeletal organization. By transcriptomics and genetic screens, we show that the solvent replacement activates two signaling pathways: (1) the heat-shock response pathway and (2) the cell integrity pathway. Although the heat-shock response system upregulates various chaperones and other stress-relieving enzymes, we find that the activation of this pathway does not offer any fitness advantage to the cells under the solvent-replaced conditions. However, limiting the D₂O-triggered activation of the cell integrity pathway allows cell growth when H₂O is completely replaced with D₂O. The isolated D₂O-tolerant strains may aid biological production of deuterated biomolecules.

Keywords: D2O; cell stress; cytokinesis; deuteration; deuterium oxide; protein folding; yeast.