Phospholipid and nucleotide syntheses are fundamental metabolic processes in eukaryotic organisms, with their dysregulation implicated in various disease states. Despite their importance, the interplay between these pathways remains poorly understood. Using genetic and metabolic analyses in Saccharomyces cerevisiae, we elucidate how cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. We find that deficiencies in the Kennedy pathway limit nucleotide salvage, prompting compensatory activation of de novo nucleotide synthesis and the pentose phosphate pathway. This metabolic shift enhances the production of antioxidants such as NADPH and glutathione. Moreover, we observe that the Kennedy pathway for phospholipid synthesis is inhibited during replicative aging, indicating its role in antioxidative defense as an adaptive mechanism in aged cells. Our findings highlight the critical role of phospholipid synthesis pathway choice in the integrative regulation of nucleotide metabolism, redox balance and membrane properties for cellular defense.

• PMID: 39060393
• DOI full text
• PubMed
• PubTator

Reference Type

Journal Article

Authors

Zhu Y, Tong X, Xue J, Qiu H, Zhang D, Zheng DQ, Tu ZC, Ye C

Primary Lit For

CHO2 | OPI3 | ZWF1 | PCT1 | ECT1 | PHM8 | DGK1 | PAH1 | CPT1 | phosphatidylcholine biosynthesis I | pentose phosphate pathway ... Show all Show fewer

Additional Lit For

Review For