Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA sequencing of ADIPOR2 knockout HEK293 cells undergone various treatments with palmitic acid

ABSTRACT: How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we used transcriptomics, lipidomics, growth and respiration assays and membrane property analyses in human HEK293 cells or human umbilical vein endothelial cells (HUVEC) to show that the function of AdipoR2 is to respond to membrane rigidification by regulating many lipid metabolism genes. We also show that AdipoR2-dependent membrane homeostasis is critical for growth and respiration in cells challenged with saturated fatty acids. Additionally, we found that AdipoR2 deficiency causes transcriptome and cell physiological defects similar to those observed in SREBP-deficient cells upon SFA challenge. Finally, we compared several genes considered important for lipid homeostasis, namely AdipoR2, SCD, FADS2, PEMT and ACSL4, and found that AdipoR2 and SCD are the most important among these to prevent membrane rigidification and excess saturation when human cells are challenged with exogenous SFAs. We conclude that AdipoR2-dependent membrane homeostasis is especially important for the non-toxic uptake of SFAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE158834 | GEO | 2021/01/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Regulation of membrane fluidity by RNF145-triggered degradation of the lipid hydrolase ADIPOR2

Project description:The regulation of membrane lipid composition is critical for cellular homeostasis. Cells are particularly sensitive to phospholipid saturation, with increased saturation causing membrane rigidification and lipotoxicity. How mammalian cells sense membrane lipid composition and reverse fatty acid (FA)-induced membrane rigidification is poorly understood. Here we systematically identify proteins that differ between mammalian cells fed saturated versus unsaturated FAs. The most differentially expressed proteins were two ER-resident polytopic membrane proteins: the E3 ubiquitin ligase RNF145 and the lipid hydrolase ADIPOR2. In unsaturated lipid membranes, RNF145 is stable, promoting its lipid-sensitive interaction, ubiquitination and degradation of ADIPOR2. When membranes become enriched in saturated FAs, RNF145 is rapidly auto-ubiquitinated and degraded, stabilising ADIPOR2, whose hydrolase activity restores lipid homeostasis and prevents lipotoxicity. We therefore identify RNF145 as a FA-responsive ubiquitin ligase which, together with ADIPOR2, define an autoregulatory pathway that controls cellular membrane lipid homeostasis and prevents acute lipotoxic stress.

2022-08-10 | PXD034835 | Pride

C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia [scRNA-seq]

Project description:While transcription factor C/AAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role on cell and metabolic homeostasis is largely unknown in cancer. Here, multi-omics analyses uncovered a coordinated activation of C/EBPα and Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism in vivo and in patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, C/EBPα regulated FASN-SCD axis to promote fatty acid (FA) biosynthesis and desaturation. We further demonstrated that FLT3 or C/EBPα inactivation decreased mono-unsaturated FAs incorporation to membrane phospholipids through SCD downregulation. Consequently, SCD inhibition enhanced susceptibility to lipid redox stress, which was exploited by combining FLT3 and glutathione peroxidase 4 inhibition to trigger lipid oxidative stress, enhancing ferroptotic death of FLT3-mutant AML cells. Altogether, our study reveals a C/EBPα function in lipid homeostasis and adaptation to redox stress, and a previously unreported vulnerability of FLT3-mutant AML to ferroptosis with promising therapeutic application.

2023-04-03 | GSE227874 | GEO

C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia [batch1-3]

2023-04-03 | GSE227839 | GEO

C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia [PDX_GILT_in vivo]

2023-04-03 | GSE226460 | GEO

C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia [PDX_QUIZ_ex vivo]

2023-04-03 | GSE226459 | GEO

C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia [MOLM14_shCEBPA+DOX]

2023-04-03 | GSE226457 | GEO

C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia [MOLM14_shCEBPAconstit]

2023-04-03 | GSE226423 | GEO

C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia [MOLM14_siCEBPA]