GO:0150175 regulation of phosphatidylethanolamine metabolic process: Lipid Homeostasis Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0150175 describes any process that modulates the frequency, rate or extent of phosphatidylethanolamine (PE) metabolic process, a central phospholipid pathway in membranes and lipoprotein biology.
• PE metabolism is essential for membrane integrity, mitochondrial function, autophagy, and humoral immunity, and its dysregulation is linked to ferroptosis, cardiovascular disease, and metabolic liver disease.
• Key regulators include enzymes of the Kennedy pathway (e.g., PCYT2, SELENOI, PEMT), PE-binding proteins, and lipid-sensing pathways that respond to nutrient and oxygen status.
• PE availability controls T follicular helper (TFH) cell differentiation and antibody responses, showing that this GO term has direct immunological relevance.
• Loss of GPX4, a glutathione peroxidase that protects against lipid peroxidation, triggers acute renal failure through ferroptosis, illustrating how PE oxidation intersects with cell death regulation.
• Experimental dissection of GO:0150175 benefits from CRISPR knockout, point-mutation, knock-in, and overexpression models combined with lipidomics, transcriptomics, and imaging.
Description
Phosphatidylethanolamine (PE) is a major zwitterionic phospholipid that shapes membrane curvature, supports mitochondrial bioenergetics, and serves as a precursor for phosphatidylcholine and other lipids. The Gene Ontology term GO:0150175, regulation of phosphatidylethanolamine metabolic process, captures the regulatory inputs that set the rate and extent of PE synthesis, remodeling, and turnover. Because PE metabolism is intertwined with one-carbon metabolism, lipoprotein assembly, and oxidative stress defense, its regulation is a focal point for researchers in cell biology, immunology, and metabolic disease. Recent work has shown that PE levels act as a metabolic checkpoint for T follicular helper cell differentiation and humoral immunity, linking phospholipid supply to adaptive immune outcomes. In parallel, dysregulated PE metabolism has been implicated in ferroptosis-dependent acute renal failure, atherosclerotic cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). These findings position GO:0150175 as a convergence node for nutrient sensing, redox balance, and membrane homeostasis. For researchers, understanding GO:0150175 means identifying the enzymes, transporters, and signaling proteins that modulate PE synthesis and consumption, and determining how their perturbation alters physiology. This article synthesizes authoritative QuickGO annotation with verified PubMed literature to outline the definition, mechanisms, key genes, disease links, and experimental strategies relevant to this term.
regulation of phosphatidylethanolamine metabolic process At A Glance
| GO ID | GO:0150175 |
|---|---|
| GO term | regulation of phosphatidylethanolamine metabolic process |
| Ontology | biological_process |
| Synonym | None listed in QuickGO |
| Major function | Modulates the frequency, rate or extent of phosphatidylethanolamine metabolic process |
| Biological context | Membrane biogenesis, mitochondrial function, lipoprotein metabolism, immune cell differentiation |
| Representative regulators | Kennedy pathway enzymes, PE-binding proteins, redox and nutrient sensors |
| Disease relevance | Ferroptosis, cardiovascular disease, MASLD, renal injury |
| Experimental approaches | CRISPR KO/point mutation/knock-in/overexpression, lipidomics, transcriptomics, imaging |
What Is GO:0150175?
GO:0150175, regulation of phosphatidylethanolamine metabolic process, is defined by QuickGO as any process that modulates the frequency, rate or extent of phosphatidylethanolamine metabolic process. In practice, this includes regulatory events that control the enzymatic steps of PE biosynthesis (such as the CDP-ethanolamine Kennedy pathway), PE remodeling by acyltransferases and phospholipases, and PE conversion to other lipids. It also encompasses signaling and transcriptional inputs that adjust PE flux in response to nutrient, redox, or hormonal cues.
Why Is regulation of phosphatidylethanolamine metabolic process Important in Cell Biology?
Regulation of phosphatidylethanolamine metabolic process is important because PE is not merely a structural lipid; it influences membrane fluidity, protein folding, mitochondrial respiration, and cell death pathways. Perturbations in PE homeostasis have been linked to ferroptosis-driven acute renal failure, atherosclerotic cardiovascular disease, and metabolic liver disease, making this GO term a hub for translational research. Moreover, PE metabolism controls T follicular helper cell responses and humoral immunity, revealing an unexpected immunological dimension. Understanding how this process is regulated can therefore inform therapeutic strategies across nephrology, cardiology, hepatology, and immunology.
• PE is a major membrane phospholipid required for cell growth and organelle function.
• Regulation of PE metabolism affects mitochondrial energy production and autophagy in the heart.
• PE availability controls T follicular helper cell differentiation and antibody responses.
• GPX4-dependent protection against PE oxidation prevents ferroptotic acute renal failure.
• PE dysfunction is associated with atherosclerotic cardiovascular disease and HDL dysfunction.
• Diet-induced RKIP downregulation disrupts PC/PE-ER homeostasis and drives MASLD.
• Bacterial PE metabolism supports survival in low-oxygen environments, highlighting evolutionary conservation.
• Metabolism-dependent succinylation can govern resource allocation for antibiotic resistance, linking PE-related metabolism to stress responses.
• PE metabolic flux is a determinant of membrane protein function and lipid droplet dynamics.
• Targeting PE regulatory nodes may offer new therapeutic opportunities in metabolic and inflammatory diseases.
What Happens During regulation of phosphatidylethanolamine metabolic process?
PE biosynthesis via the Kennedy pathway
In simple terms: Cells build PE by attaching ethanolamine to a lipid backbone in a few enzymatic steps.
The CDP-ethanolamine Kennedy pathway is the primary route for de novo PE synthesis in mammalian cells. Ethanolamine kinase phosphorylates ethanolamine, CTP:phosphoethanolamine cytidylyltransferase (PCYT2) generates CDP-ethanolamine, and CDP-ethanolamine:1,2-diacylglycerol ethanolaminephosphotransferase (CEPT1 or SELENOI) transfers phosphoethanolamine to diacylglycerol to form PE. Regulation of this pathway controls the rate of PE production and is responsive to substrate availability and hormonal signals.
PE remodeling and acyl chain exchange
In simple terms: After PE is made, enzymes swap its fatty acids to adjust membrane properties.
PE undergoes rapid remodeling through Lands cycle enzymes, including phospholipase A2 and lysophospholipid acyltransferases, which replace acyl chains to generate diverse PE molecular species. This remodeling is critical for membrane curvature, raft formation, and the generation of oxidized PE species that can trigger ferroptosis when GPX4 is compromised. Regulation of remodeling thus determines PE's functional repertoire.
PE conversion to phosphatidylcholine and other lipids
In simple terms: PE can be converted into other important lipids, especially phosphatidylcholine.
Phosphatidylethanolamine N-methyltransferase (PEMT) methylates PE to produce phosphatidylcholine (PC), a major consumer of PE in the liver. This conversion is a key branch point in phospholipid metabolism and is regulated by dietary and hormonal cues. Disruption of the PC/PE ratio in the endoplasmic reticulum contributes to metabolic dysfunction-associated steatotic liver disease (MASLD).
Redox regulation and ferroptosis protection
In simple terms: Cells protect PE from oxidative damage to avoid a type of cell death called ferroptosis.
Glutathione peroxidase 4 (GPX4) reduces oxidized PE species, preventing ferroptotic cell death. Inactivation of GPX4 in mice triggers acute renal failure, demonstrating that regulation of PE oxidation is essential for tissue survival. Thus, redox-dependent regulation of PE metabolism is a critical node in cell death and disease.
Nutrient and oxygen sensing of PE metabolism
In simple terms: Cells adjust PE metabolism based on available nutrients and oxygen.
PE metabolism is regulated by nutrient status and oxygen availability. In bacteria, PE synthesis supports life without air, indicating that oxygen tension influences PE-dependent membrane function. In mammalian cells, metabolic signals such as succinylation can modulate resource allocation and antibiotic resistance, linking PE-related metabolism to stress adaptation. These regulatory inputs ensure PE homeostasis under changing environments.
Key Genes Involved in GO:0150175 regulation of phosphatidylethanolamine metabolic process
The following genes and proteins are central to the regulation of phosphatidylethanolamine metabolic process, based on their roles in PE synthesis, remodeling, and signaling.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PCYT2 | Rate-limiting enzyme in CDP-ethanolamine Kennedy pathway | Controls de novo PE synthesis; knockout alters membrane lipid composition |
| SELENOI | CDP-ethanolamine:diacylglycerol ethanolaminephosphotransferase | Catalyzes final step of PE synthesis; mutations affect lipid metabolism |
| CEPT1 | Choline/ethanolamine phosphotransferase | Produces PE and PC; regulates phospholipid balance |
| PEMT | Phosphatidylethanolamine N-methyltransferase | Converts PE to PC; linked to liver disease and lipoprotein metabolism |
| GPX4 | Glutathione peroxidase 4 | Reduces oxidized PE; loss triggers ferroptosis and acute renal failure |
| PLA2G6 | Phospholipase A2 | Remodels PE acyl chains; involved in membrane homeostasis |
| LPCAT3 | Lysophosphatidylcholine acyltransferase 3 | Incorporates polyunsaturated fatty acids into PE; affects ferroptosis sensitivity |
| MBOAT1/2 | Membrane-bound O-acyltransferases | Contribute to PE remodeling and lipid storage |
| RKIP | Raf kinase inhibitor protein | Diet-induced downregulation disrupts PC/PE-ER homeostasis in MASLD |
| TFH-associated genes | T follicular helper cell regulators | PE metabolism controls TFH differentiation and humoral immunity |
| Mitochondrial contact proteins | ER-mitochondria tethering | Age-associated reduction impairs mitochondrial lipid metabolism and autophagy |
| Succinylation targets | Metabolic enzymes | Metabolism-dependent succinylation governs resource allocation |
| Bacterial PE synthesis enzymes | PE biosynthesis in bacteria | Support life without air; model for oxygen-independent PE function |
| HDL-associated proteins | Lipoprotein metabolism | PE regulates HDL dysfunctionality and atherosclerosis |
| Autophagy regulators | Autophagosome formation | PE metabolism supports autophagosome biogenesis in the heart |
| Ferroptosis regulators | Cell death pathways | PE oxidation is a key ferroptosis signal |
| Lipid droplet proteins | Lipid storage | PE homeostasis influences lipid droplet dynamics |
| One-carbon metabolism enzymes | Methyl donor supply | Provide methyl groups for PEMT-mediated PE methylation |
How Is regulation of phosphatidylethanolamine metabolic process Regulated?
Regulation of phosphatidylethanolamine metabolic process is exerted at multiple levels. Transcriptional control of Kennedy pathway enzymes responds to nutrient and hormonal signals. Post-translational modifications, such as succinylation, can alter enzyme activity and resource allocation. Redox status regulates GPX4 activity and PE oxidation, with glutathione availability being a key determinant. In the heart, age-associated reduction in ER-mitochondrial contacts impairs mitochondrial lipid metabolism and autophagosome formation, indirectly affecting PE homeostasis. Additionally, diet-induced changes in RKIP expression disrupt PC/PE-ER homeostasis, linking nutritional status to PE regulation.
regulation of phosphatidylethanolamine metabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| GPX4 | Ferroptosis, acute renal failure | Gpx4 knockout mouse; renal ischemia-reperfusion model |
| PEMT | MASLD, lipoprotein disorders | Pemt knockout mouse; high-fat diet challenge |
| RKIP | MASLD, PC/PE-ER homeostasis | RKIP knockout or overexpression in hepatocytes |
| HDL-associated proteins | Atherosclerotic cardiovascular disease | ApoE knockout mouse; PE supplementation |
| TFH regulators | Humoral immunity | T cell-specific knockout; immunization models |
Ferroptosis and acute renal failure
GPX4 inactivation leads to accumulation of oxidized PE species and ferroptotic cell death, causing acute renal failure in mice. This establishes regulation of PE metabolism as a critical determinant of kidney injury and a potential therapeutic target.
Cardiovascular disease and atherosclerosis
PE regulates HDL functionality and links polyunsaturated fatty acids to atherosclerotic cardiovascular diseases. Dysregulated PE metabolism may contribute to lipoprotein dysfunction and plaque formation.
Metabolic dysfunction-associated steatotic liver disease (MASLD)
Diet-induced RKIP downregulation disrupts PC/PE-ER homeostasis, driving MASLD. This highlights the importance of PE regulation in liver lipid handling and disease progression.
Immunity and humoral responses
PE metabolism controls T follicular helper cell differentiation and humoral immunity, suggesting that dysregulation could impact vaccine responses and autoimmune conditions.
From regulation of phosphatidylethanolamine metabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of PCYT2 alter PE synthesis and membrane composition? | CRISPR knockout of PCYT2 in HEK293 or HepG2 cells |
| Does a point mutation in GPX4 affect ferroptosis sensitivity? | CRISPR point mutation (e.g., active-site cysteine) in GPX4 |
| Can PE-binding domain tagging reveal localization? | Knock-in of fluorescent tag at endogenous PE-binding protein locus |
| Does overexpression of SELENOI increase PE levels? | Doxycycline-inducible overexpression in mammalian cells |
| How does RKIP downregulation affect PC/PE ratio? | CRISPR knockout or siRNA in hepatocytes |
| Does loss of ER-mitochondria contacts alter PE metabolism? | Knockout of tethering proteins in cardiomyocytes |
How to Study the regulation of phosphatidylethanolamine metabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| LC-MS/MS lipidomics | PE species and oxidized PE | Quantify PE changes in knockout cells |
| RNA-seq | Transcript levels of PE metabolic genes | Assess transcriptional regulation |
| Proteomics | Protein abundance and modifications | Identify succinylated enzymes |
| Fluorescence microscopy | PE localization and organelle morphology | Visualize ER-mitochondria contacts |
| CRISPR screening | Genes affecting PE homeostasis | Discover novel regulators |
| Western blot | Protein expression of GPX4, PEMT, etc. | Validate knockout efficiency |
| Seahorse assay | Mitochondrial respiration | Link PE metabolism to bioenergetics |
| Flow cytometry | TFH cell differentiation | Assess immune effects of PE perturbation |
Lipidomics and mass spectrometry
Targeted lipidomics using LC-MS/MS quantifies PE species and their oxidized forms, providing direct readouts of PE metabolic flux. This method is essential for validating CRISPR models.
Transcriptomics and RNA-seq
RNA-seq measures expression changes in Kennedy pathway enzymes and related regulators upon genetic perturbation, revealing transcriptional responses.
Proteomics and post-translational modification analysis
Proteomics can identify succinylation and other modifications on PE metabolic enzymes, linking metabolic state to enzyme activity.
Imaging and fluorescent reporters
Fluorescent PE-binding probes and organelle markers allow visualization of PE distribution and membrane dynamics in live cells.
How CRISPR Can Be Used to Study GO:0150175 regulation of phosphatidylethanolamine metabolic process
Knockout
CRISPR knockout of genes such as PCYT2, SELENOI, or GPX4 enables loss-of-function studies to determine their role in PE metabolism and downstream phenotypes like ferroptosis. Knockout models are foundational for causal inference.
Point Mutation
Introducing specific point mutations (e.g., catalytic residues in GPX4 or PEMT) allows dissection of enzymatic activity versus scaffolding functions without completely abolishing protein expression.
Knock-in
Knock-in of epitope tags or fluorescent proteins at endogenous loci facilitates tracking of PE metabolic enzymes and their interactors in real time.
Overexpression
Overexpression of rate-limiting enzymes like PCYT2 or SELENOI can increase PE synthesis, enabling gain-of-function studies and testing of therapeutic hypotheses.
How EDITGENE Supports regulation of phosphatidylethanolamine metabolic process Research
Researchers studying regulation of phosphatidylethanolamine metabolic process-related genes often need to determine whether a candidate gene is causally involved in PE homeostasis, membrane function, or disease phenotypes. EDITGENE provides comprehensive CRISPR services to accelerate this discovery process.
Contact EDITGENE today to design your custom CRISPR model for regulation of phosphatidylethanolamine metabolic process research.
Frequently Asked Questions About regulation of phosphatidylethanolamine metabolic process
What is GO:0150175?
GO:0150175 is the Gene Ontology term for regulation of phosphatidylethanolamine metabolic process, defined as any process that modulates the frequency, rate or extent of phosphatidylethanolamine metabolic process.
What genes are involved in regulation of phosphatidylethanolamine metabolic process?
Key genes include PCYT2, SELENOI, CEPT1, PEMT, GPX4, and LPCAT3, which control PE synthesis, remodeling, and oxidation.
Why is phosphatidylethanolamine metabolism important?
PE is essential for membrane integrity, mitochondrial function, and immunity; its dysregulation is linked to ferroptosis, cardiovascular disease, and MASLD.
How is phosphatidylethanolamine synthesized?
PE is primarily synthesized via the CDP-ethanolamine Kennedy pathway, involving PCYT2 and SELENOI.
What diseases are associated with PE metabolism?
Ferroptosis-related acute renal failure, atherosclerosis, and metabolic liver disease are associated with PE dysregulation.
How can I study regulation of PE metabolism?
CRISPR knockout, point mutation, knock-in, and overexpression models combined with lipidomics and transcriptomics are effective approaches.
Does PE metabolism affect the immune system?
Yes, PE metabolism controls T follicular helper cell differentiation and humoral immunity.
What is the role of GPX4 in PE metabolism?
GPX4 reduces oxidized PE species, preventing ferroptotic cell death; its inactivation causes acute renal failure in mice.
Can CRISPR be used to study PE metabolism?
Yes, CRISPR knockout and knock-in models are widely used to dissect PE metabolic gene function.
What is the link between PE and MASLD?
Diet-induced RKIP downregulation disrupts PC/PE-ER homeostasis, driving MASLD.
Conclusion
Regulation of phosphatidylethanolamine metabolic process (GO:0150175) is a critical biological process that integrates lipid synthesis, membrane dynamics, redox balance, and immune signaling. Dysregulation of PE metabolism contributes to ferroptosis, cardiovascular disease, and metabolic liver disease, making it a compelling target for basic and translational research. Advances in CRISPR-based models and lipidomics will continue to illuminate the regulatory networks controlling PE homeostasis. EDITGENE offers a full suite of services to support these investigations.
References
- 1. Fu G et al.. 2021. Metabolic control of T(FH) cells and humoral immunity by phosphatidylethanolamine.. Nature 595(7869):724-729 PMID: 34234346
- 2. Friedmann Angeli JP et al.. 2014. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice.. Nat Cell Biol 16(12):1180-91 PMID: 25402683
- 3. van der Veen JN et al.. 2017. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease.. Biochim Biophys Acta Biomembr 1859(9 Pt B):1558-1572 PMID: 28411170
- 4. Wu JH et al.. 2025. Metabolism-dependent succinylation governs resource allocation for antibiotic resistance.. Sci Adv 11(34):eadu2856 PMID: 40845110
- 5. Taradeh M et al.. 2026. Regulation of HDL dysfunctionality by phosphatidylethanolamine links poly-unsaturated fatty acids with atherosclerotic cardiovascular diseases.. Mol Metab 103:102281 PMID: 41248752
- 6. Goldfine H. 2020. Life without air.. J Biol Chem 295(13):4124-4133 PMID: 32221031
- 7. Li M et al.. 2025. Diet-induced RKIP downregulation disrupts PC/PE-ER homeostasis to drive MASLD.. Nat Commun 16(1):11092 PMID: 41387436
- 8. Hong W et al.. 2025. Age-associated reduction in ER-Mitochondrial contacts impairs mitochondrial lipid metabolism and autophagosome formation in the heart.. Cell Death Differ 32(10):1900-1914 PMID: 40254645
