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Glycerol-3-phosphate and Phosphoethanolamine homeostatic switch triggers senescence by rewiring lipid metabolism II

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE248823 | GEO | 2024/02/01

REPOSITORIES: GEO

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Project description:A systems biology study of two distinct growth phases of Saccharomyces cerevisiae cultures AM Martins, D Camacho, J Shuman, W Sha, P Mendes, V Shulaev, Current Genomics 2004 5:649-663 This is a model of yeast glycolysis and glycerol synthesis for high medium glucose concentration. It was constructed by joining the glycolysis model of Teusink et al. (2000) Eur J Biochem 267, 5313, modified by Pritchard and Kell (2002) Eur. J. Biochem. 269, 3894, with the glycerol synthesis model of Crownright et al. (2002) Appl. Env. Microbiol. 68, 4448. Glycerol transport was added as a first order reaction with parameters that comply with empirical data on internal/external glycerol ratios. Curation notes The model provided by the authors is available from http://www.mcisb.org/resources/models/martins04_original.xml . It contains one error: the kinetic law of glycerol 3-phosphate dehydrogenase has denominator of the form (1+NADH/Kdhap+NAD/Kg3p)*(1+DHAP/Knadh+G3P/Knad) rather than (1+DHAP/Kdhap+G3P/Kg3p)*(1+NADH/Knadh+NAD/Knad). This has now been corrected; steady states of the original model may be resolved by exchanging the order of substrates and products in COPASI . Some other cosmetic changes (e.g minutes to seconds) have also been carried out. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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Glycerol-3-phosphate and Phosphoethanolamine homeostatic switch triggers senescence by rewiring lipid metabolism II

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