Glycerol-3-phosphate and Phosphoethanolamine homeostatic switch triggers senescence by rewiring lipid metabolism
Creators
- Tighanimine, Khaled
- Freitas, José-Américo Nabuco Leva Ferreira
- Nemazanyy, Ivan
- Bankolé, Alexia
- Benarroch-Popivker, Delphine
- Brodesser, Susanne
- Doré, Gregory
- Robinson, Lucas
- Benit, Paule
- Ladraa, Sophia
- Bou Saada, Yara
- Friguet, Bertrand
- Bertolino, Philippe
- Bernard, David
- Canaud, Guillaume
- Rustin, Pierre
- Gilson, Eric
- Bischof, Oliver
- Fumagalli, Stefano
- Pende, Mario
Description
Cellular senescence impacts many physiological and pathological processes. A durable cell cycle arrest, inflammatory secretory phenotype, and metabolic reprogramming characterize it. Identifying common and specific metabolic liabilities in senescence provide novel inroads to exploit senescence targeting for health benefits. Here, we use dynamic transcriptome and metabolome profiling in different senescence subtypes to reveal common and specific metabolic signatures. Specifically, we pinpoint the homeostatic switch of glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) accumulation, intimately linking lipid metabolism to the senescence gene expression program. Mechanistically, p53-dependent glycerol kinase (GK) activation and post-translational inactivation of Phosphate Cytidylyltransferase 2- Ethanolamine (PCYT2) regulate this metabolic switch, which is senogenic. Conversely, G3P phosphatase (G3PP) and Ethanolamine-Phosphate Phospho-Lyase (ETNPPL)-based scavenging of G3P and PEtn is senomorphic.
Collectively, our study ties the G3P-PEtn homeostatic switch to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential, novel therapeutic avenue for senescence targeting in pathophysiology.
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Additional details
Related works
- Is variant form of
- Dataset: GSE248822 (Other)