Phospholipid Biosynthesis: An Unforeseen Modulator of Nuclear Metabolism

Glycerophospholipid biosynthesis is crucial not only for providing structural components required for membrane biogenesis during cell proliferation but also for facilitating membrane remodeling under stress conditions. The biosynthetic pathways for glycerophospholipid tails, glycerol backbones, and diverse head group classes intersect with various other metabolic processes, sharing intermediary metabolites. Recent studies have revealed intricate connections between glycerophospholipid synthesis and nuclear metabolism, including metabolite-mediated crosstalk with the epigenome, signaling pathways that govern genome integrity, and CTP-involved regulation of nucleotide and antioxidant biosynthesis. This review highlights recent advances in understanding the functional roles of glycerophospholipid biosynthesis beyond their structural functions in budding yeast and mammalian cells. We propose that glycerophospholipid biosynthesis plays an integrative role in metabolic regulation, providing a new perspective on lipid biology.