Reciprocal regulation of phosphatidylcholine synthesis and H3K36 methylation programs metabolic adaptation II
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE193198 | GEO | 2023/04/01
REPOSITORIES: GEO
Similar Datasets
Project description:Our findings demonstrated how phospholipid metabolism enabled metabolic transformation through an epigenetic modification, illuminating an underappreciated metabolic intersection for environmental adaptation in eukaryotic cells.
2023-08-04 | GSE181620 | GEO
Project description:Reciprocal regulation of phosphatidylcholine synthesis and H3K36 methylation programs metabolic adaptation
| PRJNA752757 | ENA
Project description:Reciprocal regulation of phosphatidylcholine synthesis and H3K36 methylation programs metabolic adaptation II
| PRJNA795416 | ENA
Project description:Phospholipid and nucleotide syntheses are fundamental metabolic processes in eukaryotic organisms, with their dysregulation implicated in various disease states. However, the interplay between these pathways remains elusive. With genetic and metabolic analyses in the yeast S. cerevisiae, we elucidate how cytidine triphosphate utilization and recycling in the Kennedy pathway for phospholipid synthesis influence nucleotide metabolism and redox balance. Deficiencies in the Kennedy pathway impose constraints on nucleotide salvage, prompting compensatory co-activation of de novo nucleotide synthesis and the pentose phosphate pathway. Consequently, this metabolic shift towards alternative nucleotide and phospholipid synthesis pathways fosters the production of antioxidants such as NADPH and glutathione. Additionally, we observe that this oxidation-responsive Kennedy pathway for phospholipid synthesis is inhibited during replicative aging, highlighting its activation as an antioxidative defense mechanism in aged cells. These findings underscore the critical role of pathway choice in phospholipid synthesis in the integrative regulation of nucleotide metabolism, redox balance, and membrane biophysical properties for cellular defense.
2024-07-25 | GSE269277 | GEO
Project description:Phospholipid and nucleotide syntheses are fundamental metabolic processes in eukaryotic organisms, with their dysregulation implicated in various disease states. However, the interplay between these pathways remains elusive. With genetic and metabolic analyses in the yeast S. cerevisiae, we elucidate how cytidine triphosphate utilization and recycling in the Kennedy pathway for phospholipid synthesis influence nucleotide metabolism and redox balance. Deficiencies in the Kennedy pathway impose constraints on nucleotide salvage, prompting compensatory co-activation of de novo nucleotide synthesis and the pentose phosphate pathway. Consequently, this metabolic shift towards alternative nucleotide and phospholipid synthesis pathways fosters the production of antioxidants such as NADPH and glutathione. Additionally, we observe that this oxidation-responsive Kennedy pathway for phospholipid synthesis is inhibited during replicative aging, highlighting its activation as an antioxidative defense mechanism in aged cells. These findings underscore the critical role of pathway choice in phospholipid synthesis in the integrative regulation of nucleotide metabolism, redox balance, and membrane biophysical properties for cellular defense.
2024-07-25 | GSE269275 | GEO
Project description:Renal endothelial cells (RECs) from glomerular cortical and medullary kidney compartments are exposed to different microenvironmental conditions. Upon dehydration medullary RECs (mRECs) are exposed to extreme hyperosmolarity. However the heterogeneous phenotypes of RECs remain in-completely inventoried and how mRECs respond to dehydration is unknown. By single cell RNA-sequencing of >40000 RECs we identified 24 (including 8 novel) REC phenotypes highlighting extensive heterogeneity of RECs between and within the cortex glomeruli and medulla. In response to dehydration mRECs upregulated primarily the expression of genes involved in the hypoxia response glycolysis and surprisingly oxidative phosphorylation (OXPHOS). In vitro mRECs increased oxygen consumption in response to hyperosmolarity presumably to sustain ATP production for Na+/K+ ATPase pump-mediated salt excretion and to generate metabolic water during OXPHOS in order to counteract mREC hyperosmolarity unveiling a previously underappreciated role of OXPHOS. Overall RECs exhibit extensive heterogeneity and plasticity to adapt their metabolic transcriptome to overcome dehydration.
2019-12-12 | E-MTAB-8145 | biostudies-arrayexpress
Project description:Cell membrane phosphatidylcholine composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in membrane phosphatidylcholine saturation are implicated in metabolic disorders. Here, we identified LPCAT3 as the major isoform of LPCAT in adipose tissues and created adipocyte-specific Lpcat3-knockout mice to study adipose tissue lipid metabolism. Transcriptome sequencing and plasma adipokine profiling were used to investigate how LPCAT3 regulates adipose tissue insulin signaling. LPCAT3 deficiency reduced polyunsaturated phosphatidylcholines in adipocyte plasma membranes, increasing insulin sensitivity. LPCAT3 deficiency influenced membrane lipid rafts, which activated insulin receptors and AKT in adipose tissue, and attenuated diet-induced insulin resistance. Conversely, higher LPCAT3 activity in adipose tissues from ob/ob, db/db, and high-fat diet-fed mice reduced insulin signaling. Adding polyunsaturated phosphatidylcholines to mature human or mouse adipocytes in vitro worsened insulin signaling. We suggest that targeting LPCAT3 in adipose tissues to manipulate membrane phospholipid saturation is a new strategy to treat insulin resistance.
2024-07-16 | GSE234884 | GEO
Project description:Cell membrane phosphatidylcholine composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in membrane phosphatidylcholine saturation are implicated in metabolic disorders. Here, we identified LPCAT3 as the major isoform of LPCAT in adipose tissues and created adipocyte-specific Lpcat3-knockout mice to study adipose tissue lipid metabolism. Transcriptome sequencing and plasma adipokine profiling were used to investigate how LPCAT3 regulates adipose tissue insulin signaling. LPCAT3 deficiency reduced polyunsaturated phosphatidylcholines in adipocyte plasma membranes, increasing insulin sensitivity. LPCAT3 deficiency influenced membrane lipid rafts, which activated insulin receptors and AKT in adipose tissue, and attenuated diet-induced insulin resistance. Conversely, higher LPCAT3 activity in adipose tissues from ob/ob, db/db, and high-fat diet-fed mice reduced insulin signaling. Adding polyunsaturated phosphatidylcholines to mature human or mouse adipocytes in vitro worsened insulin signaling. We suggest that targeting LPCAT3 in adipose tissues to manipulate membrane phospholipid saturation is a new strategy to treat insulin resistance.
2024-07-16 | GSE235302 | GEO
Project description:All free-living microorganisms homeostatically maintain the fluidity of their membranes by adapting lipid composition to environmental temperatures. A quantitative description of how organisms maintain constant fluidity at all growth temperatures has not been achieved. By quantifying both enzymes and metabolic intermediates of the Escherichia coli fatty acid and phospholipid synthesis pathways, we discover how E. coli measures steady-state temperature and restores optimal membrane fluidity within a single generation after temperature shocks.
2024-10-10 | PXD051802 | Pride
Project description:Sen2013 - Phospholipid Synthesis in P.knowlesi
The model describes the multiple phospholipid synthetic pathways in Plasmodium knowlesi.
This model is described in the article:
Kinetic modelling of phospholipid synthesis in Plasmodium knowlesi unravels crucial steps and relative importance of multiple pathways.
Sen P, Vial HJ, Radulescu O.
BMC Syst Biol 2013 Nov; 7(1): 123
Abstract:
BACKGROUND: Plasmodium is the causal parasite of malaria, infectious disease responsible for the death of up to one million people each year. Glycerophospholipid and consequently membrane biosynthesis are essential for the survival of the parasite and are targeted by a new class of antimalarial drugs developed in our lab. In order to understand the highly redundant phospholipid synthethic pathways and eventual mechanism of resistance to various drugs, an organism specific kinetic model of these metabolic pathways need to be developed in Plasmodium species. RESULTS: Fluxomic data were used to build a quantitative kinetic model of glycerophospholipid pathways in Plasmodium knowlesi. In vitro incorporation dynamics of phospholipids unravels multiple synthetic pathways. A detailed metabolic network with values of the kinetic parameters (maximum rates and Michaelis constants) has been built. In order to obtain a global search in the parameter space, we have designed a hybrid, discrete and continuous, optimization method. Discrete parameters were used to sample the cone of admissible fluxes, whereas the continuous Michaelis and maximum rates constants were obtained by local minimization of an objective function.The model was used to predict the distribution of fluxes within the network of various metabolic precursors.The quantitative analysis was used to understand eventual links between different pathways. The major source of phosphatidylcholine (PC) is the CDP-choline Kennedy pathway.In silico knock-out experiments showed comparable importance of phosphoethanolamine-N-methyltransferase (PMT) and phosphatidylethanolamine-N-methyltransferase (PEMT) for PC synthesis.The flux values indicate that, major part of serine derived phosphatidylethanolamine (PE) is formed via serine decarboxylation, whereas major part of phosphatidylserine (PS) is formed by base-exchange reactions.Sensitivity analysis of CDP-choline pathway shows that the carrier-mediated choline entry into the parasite and the phosphocholine cytidylyltransferase reaction have the largest sensitivity coefficients in this pathway, but does not distinguish a reaction as an unique rate-limiting step.
CONCLUSION: We provide a fully parametrized kinetic model for the multiple phospholipid synthetic pathways in P. knowlesi. This model has been used to clarify the relative importance of the various reactions in these metabolic pathways. Future work extensions of this modelling strategy will serve to elucidate the regulatory mechanisms governing the development of Plasmodium during its blood stages, as well as the mechanisms of action of drugs on membrane biosynthetic pathways and eventual mechanisms of resistance.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000495
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
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.
2024-09-02 | BIOMD0000000495 | BioModels