Inorganic phosphate is an essential nutrient acquired by cells from their environment and assimilated into myriad intracellular metabolites and macromolecules. Here we characterize the metabolic responses of fission yeast to a 24-h interval of phosphate starvation, during which cells enter a state of G0 quiescence. Time-resolved profiling revealed that many key phosphometabolites were progressively depleted, including: (i) NTPs, NDPs, and dNTPs; (ii) coenzyme A, NAD+, NADP+, NADH, and ADP-ribose; (iii) glycolysis pathway intermediates upstream of pyruvate; (iv) pentose phosphate pathway intermediates from 6-phosphogluconate to sedoheptulose-7-phosphate; (v) nucleotide sugars GDP-glucose/mannose, UDP-glucose/galactose, and UDP-GalNAc/GluNAc; and (vi) phospholipid precursors glycerol-3-phosphate, CDP-choline, and glycerophosphocholine. By contrast, early Krebs cycle intermediates accumulated during phosphate starvation. Other metabolic changes included: (i) interdiction of de novo pyrimidine synthesis; (ii) depletion of S-adenosylmethionine and S-adenosylhomocysteine; (iii) transient accumulation of polyamine biosynthetic intermediates putrescine, S-adenosylmethioninamine and 5-methylthioadenosine; (iv) accumulation of betaine (correlating with an increase in expression of atd1 mRNA encoding aldehyde dehydrogenase); and (v) depletion of aminoadipate pathway intermediates 2-oxoadipate, 2-aminoadipate and saccharopine. Replenishing phosphate after 24 h of starvation resulted in restoration of the metabolite levels to similar levels as non-starved controls (over 2 to 12 h) as cells exited quiescence and resumed growth.
[doi:10.25345/C50G3H96M]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: phosphate metabolism ; phosphate starvation ; Schizosaccharomyces pombe ; DatasetType:Metabolomics
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Stewart Shuman, Memorial Sloan Kettering Cancer Center, United States of America |
Submitting User: | rubenjjframos |
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Owner | Reanalyses | |
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