Abstract: |
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-hexose, UDP-glucose/galactose, and UDP-GalNAc/GlcNAc; 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 the following: (i) interdiction of de novo pyrimidine synthesis; (ii) depletion of S-adenosylmethionine and S-adenosylhomocysteine; (iii) transient accumulation of polyamine biosynthetic intermediates putrescine 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 pre-starvation metabolome (over 2 to 12 h) as cells exited quiescence and resumed growth. Copyright © 2025 Sanchez et al. |