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Phospholipid biosynthesis modulates nucleotide metabolism and reductive capacity
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Journal Article
Phospholipid biosynthesis modulates nucleotide metabolism and reductive capacity
2025
Overview
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.
Zhu et al. found that cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. Phospholipid synthesis acts as an integrative defense mechanism to sense and combat oxidative stress.
Publisher
Nature Publishing Group US,Nature Publishing Group
