sb9b00376_si_001.pdf (541.44 kB)
Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water
journal contribution
posted on 2020-03-18, 14:36 authored by Caroline Kampmeyer, Jens V. Johansen, Christian Holmberg, Magnus Karlson, Sarah K. Gersing, Heloisa N. Bordallo, Birthe B. Kragelund, Mathilde H. Lerche, Isabelle Jourdain, Jakob R. Winther, Rasmus Hartmann-PetersenLife 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.
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D 2 O-tolerant strainscell growthD 2 Osolvent-replaced conditionsgrowth retardationD 2 O-triggered activationheat-shock response pathwaySingle Signaling Pathwaycytoskeletal organizationH 2 Oreplacement activatesstress-relieving enzymescell wallsCell Growthfitness advantageheat-shock response system upregulatesmodel organismSchizosaccharomyces pombecell integrity pathwayglucose metabolismHeavy Water Life
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