A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism.

ABSTRACT: Cellular senescence affects many physiological and pathological processes and is characterized by durable cell cycle arrest, an inflammatory secretory phenotype and metabolic reprogramming. Here, by using dynamic transcriptome and metabolome profiling in human fibroblasts with different subtypes of senescence, we show that a homoeostatic switch that results in glycerol-3-phosphate (G3P) and phosphoethanolamine (pEtN) accumulation links lipid metabolism to the senescence gene expression programme. Mechanistically, p53-dependent glycerol kinase activation and post-translational inactivation of phosphate cytidylyltransferase 2, ethanolamine regulate this metabolic switch, which promotes triglyceride accumulation in lipid droplets and induces the senescence gene expression programme. Conversel

SUBMITTER: Tighanimine K 

PROVIDER: S-EPMC10896726 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature