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

Area of Science:

• Biochemistry
• Cell Biology
• Microbiology

Background:

• Water is essential for all known life.
• Heavy water (D2O) is an isotopologue of water with distinct physical and chemical properties.
• Understanding biological responses to D2O can reveal insights into water's fundamental role.

Purpose of the Study:

• To investigate the biological effects of replacing water with heavy water (D2O) in the model organism Schizosaccharomyces pombe.
• To identify cellular pathways and mechanisms involved in D2O tolerance.

Main Methods:

• Culturing Schizosaccharomyces pombe in varying concentrations of D2O.
• Assessing cellular growth, metabolism (glucose), morphology, and cytoskeletal organization.
• Employing transcriptomics and genetic screens to analyze cellular responses.

Main Results:

• High D2O concentrations induced growth retardation, altered glucose metabolism, morphological changes, thickened cell walls, and aberrant cytoskeleton.
• Solvent replacement activated the heat-shock response and cell integrity pathways.
• Heat-shock response activation did not confer a fitness advantage.
• Limiting cell integrity pathway activation enabled growth in complete D2O.

Conclusions:

• The cell integrity pathway is crucial for adaptation to heavy water (D2O).
• D2O-tolerant strains of Schizosaccharomyces pombe can be developed by modulating this pathway.
• These findings support the potential for biological production of deuterated biomolecules.