Necker Institute, Medicine Faculty, Paris
"A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism" Nature Metabolism 6, 323–342. https://doi.org/10.1038/s42255-023-00972-y
Khaled Tighanimine, José Américo Nabuco Leva Ferreira Freitas, Ivan Nemazanyy, Alexia Bankolé, Delphine Benarroch-Popivker, Susanne Brodesser, Gregory Doré, Lucas Robinson, Paule Benit, Sophia Ladraa, Yara Bou Saada, Bertrand Friguet, Philippe Bertolino, David Bernard, Guillaume Canaud, Pierre Rustin, Eric Gilson, Oliver Bischof, Stefano Fumagalli & Mario Pende (2024)
Cv
After obtaining a scientific baccalaureate in Algiers, Khaled Tighanimine (28 years old) pursued his higher education (bachelor's - master's) in biology at Sorbonne University in France. He initially worked on the role of non-coding RNAs in the spatial conformation of Escherichia coli nucleoids at the Collège de France within Olivier Espéli's team. He then joined Mario Pende's team at the Institut Necker Enfants Malades to complete his doctorate on the metabolism of senescent cells. He defended his thesis in November 2023 and is continuing the project in its in vivo phase for 10 months as a postdoc, before joining Brendan Manning's lab at Harvard T.H School of Public Health to to fulfil his interest in metabolism.
Contact
Khaled Thiganimine
Institut Necker Enfants Malades - Faculté de Médecine, 160 Rue de Vaugirard 156, 75015 Paris
Mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
Twitter: @khaledtigha
Résumé de l'article
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. Conversely, G3P phosphatase and ethanolamine-phosphate phospho-lyase-based scavenging of G3P and pEtN acts in a senomorphic way by reducing G3P and pEtN accumulation. Collectively, our study ties G3P and pEtN accumulation to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential therapeutic avenue for targeting senescence and related pathophysiology.
