GO:0036155 acylglycerol acyl-chain remodeling: Lipid Remodeling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0036155 acylglycerol acyl-chain remodeling describes the sequential deacylation and re-acylation of acylglycerols to generate molecules with different fatty acid acyl chains.
• This process is essential for membrane lipid remodeling in plants and for maintaining membrane trafficking and enzymatic processing of lipids in eukaryotic cells.
• Key enzymes include lipases such as DDHD2, which possesses both lipase and transacylase capacities to remodel triglyceride acyl chains.
• Acyltransferases like LYCAT and LPLAT10/LPEAT2 control specific phosphoinositides and synthesize phosphatidylcholine with very-long-chain fatty acids.
• DGAT-mediated lipid droplet biogenesis and acyl-chain remodeling influence ferroptosis sensitivity, linking this process to cell death regulation.
• Stable isotopic labeling has revealed carbon and acyl chain flux during stress-induced triglyceride accumulation in microalgae.
Description
Acylglycerol acyl-chain remodeling (GO:0036155) is a biological process that modifies the fatty acid composition of acylglycerols through sequential deacylation and re-acylation reactions. This remodeling generates acylglycerols containing different types of fatty acid acyl chains, which is critical for adjusting membrane lipid properties and cellular functions. The process is conserved across eukaryotes and plays a central role in membrane lipid remodeling in plants, where it helps maintain membrane integrity under stress. In mammalian cells, acyl-chain remodeling influences lipid droplet composition, membrane trafficking, and the enzymatic processing of lipids. Recent studies have identified specific enzymes, such as DDHD2, that catalyze both lipase and transacylase reactions to remodel triglyceride acyl chains. Understanding this process is important for researchers studying lipid metabolism, membrane dynamics, and diseases linked to lipid dysfunction.
acylglycerol acyl-chain remodeling At A Glance
| GO ID | GO:0036155 |
|---|---|
| GO term | acylglycerol acyl-chain remodeling |
| Ontology | biological_process |
| Synonym | acylglycerol acyl-chain remodelling, glyceride acyl-chain remodeling |
| Major function | Remodeling acyl chains of acylglycerols via deacylation and re-acylation to generate different fatty acid compositions |
| Related processes | Membrane lipid remodeling, lipid droplet biogenesis, triglyceride metabolism |
| Key enzymes | Lipases (e.g., DDHD2), acyltransferases (e.g., LYCAT, LPLAT10/LPEAT2) |
| Cellular context | Membranes, lipid droplets, and lipoprotein particles |
What Is GO:0036155?
Acylglycerol acyl-chain remodeling is the process of changing the fatty acid chains attached to a glycerol backbone in acylglycerols. It occurs through a cycle of removing existing acyl chains (deacylation) and adding new ones (re-acylation), resulting in acylglycerols with different types of fatty acid acyl chains. This definition is based on the Gene Ontology term GO:0036155.
Why Is acylglycerol acyl-chain remodeling Important in Cell Biology?
Acylglycerol acyl-chain remodeling is fundamental for maintaining membrane lipid composition and function, which affects membrane trafficking, enzymatic processing of lipids, and cellular responses to stress. Dysregulation of this process is linked to metabolic disorders, neurodegeneration, and cancer, making it a key area for therapeutic research.
• Maintains membrane fluidity and permeability by adjusting acyl chain composition.
• Regulates lipid droplet size and composition, influencing energy storage and release.
• Controls ferroptosis sensitivity through DGAT-mediated lipid droplet biogenesis.
• Supports membrane trafficking by controlling specific phosphoinositides via LYCAT.
• Enables synthesis of very-long-chain fatty acid-containing phosphatidylcholine, relevant to X-linked adrenoleukodystrophy.
• Facilitates stress-induced triglyceride accumulation in microalgae.
• Impacts enzymatic processing of lipids by altering acyl chain dynamics.
• Provides precursors for signaling lipids and membrane remodeling in plants.
What Happens During acylglycerol acyl-chain remodeling?
Deacylation: Removal of Existing Acyl Chains
In simple terms: First, enzymes remove fatty acid chains from the glycerol backbone.
Deacylation is catalyzed by lipases that hydrolyze acyl chains from acylglycerols. For example, DDHD2 acts as a lipase to remove acyl chains from triglycerides, initiating remodeling. This step generates lysoglycerolipids or diacylglycerols that can be further modified.
Re-acylation: Addition of New Acyl Chains
In simple terms: Next, new fatty acid chains are attached to the glycerol backbone.
Re-acylation is mediated by acyltransferases that transfer acyl chains from acyl-CoA or other donors to lysoglycerolipids. LYCAT controls specific phosphoinositides by re-acylating them, while LPLAT10/LPEAT2 synthesizes phosphatidylcholine with C26:0 moiety. DDHD2 also possesses transacylase activity, directly transferring acyl chains to remodel triglycerides.
Substrate Specificity and Acyl Chain Selection
In simple terms: The enzymes choose which fatty acids to add or remove.
Acyl-chain remodeling enzymes exhibit specificity for certain fatty acids and lipid headgroups. For instance, LYCAT specifically remodels phosphoinositides, and LPLAT10/LPEAT2 prefers very-long-chain fatty acids like C26:0. This specificity ensures that acylglycerols acquire the appropriate acyl composition for their cellular functions.
Integration with Lipid Droplet Biogenesis
In simple terms: Remodeling helps build and modify lipid droplets.
Acyl-chain remodeling is closely linked to lipid droplet formation. DGAT enzymes catalyze the final step of triglyceride synthesis, and their activity influences lipid droplet biogenesis and ferroptosis sensitivity. Remodeling of triglycerides within lipid droplets affects their packing and stability.
Stress-Induced Remodeling in Plants and Microalgae
In simple terms: Under stress, cells remodel acyl chains to store energy or protect membranes.
In plants, membrane lipid remodeling is crucial for acclimation to environmental stress. In microalgae like Coccomyxa subellipsoidea, stable isotopic labeling revealed carbon and acyl chain flux during stress-induced triglyceride accumulation. This highlights the role of remodeling in energy storage and stress responses.
Key Genes Involved in GO:0036155 acylglycerol acyl-chain remodeling
The following genes and proteins are key players in acylglycerol acyl-chain remodeling, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| DDHD2 | Lipase and transacylase that remodels triglyceride acyl chains | Studied for its dual enzymatic activities in lipid remodeling |
| LYCAT | Acyltransferase controlling specific phosphoinositides | Regulates membrane traffic and phosphoinositide composition |
| LPLAT10/LPEAT2 | Synthesizes phosphatidylcholine with C26:0 moiety | Linked to X-linked adrenoleukodystrophy diagnostics |
| DGAT1 | Diacylglycerol acyltransferase, catalyzes triglyceride synthesis | Influences lipid droplet biogenesis and ferroptosis sensitivity |
| DGAT2 | Diacylglycerol acyltransferase, catalyzes triglyceride synthesis | Influences lipid droplet biogenesis and ferroptosis sensitivity |
| PNPLA2 | Lipase involved in triglyceride hydrolysis | Potential role in deacylation steps of remodeling |
| ABHD5 | Co-activator of PNPLA2 lipase | Regulates lipolysis and acyl-chain remodeling |
| MOGAT1 | Monoacylglycerol acyltransferase | May contribute to re-acylation in remodeling |
| MOGAT2 | Monoacylglycerol acyltransferase | May contribute to re-acylation in remodeling |
| LPCAT1 | Lysophosphatidylcholine acyltransferase | Involved in phospholipid remodeling |
| LPCAT2 | Lysophosphatidylcholine acyltransferase | Involved in phospholipid remodeling |
| LPCAT3 | Lysophosphatidylcholine acyltransferase | Involved in phospholipid remodeling |
| LPEAT1 | Lysophosphatidylethanolamine acyltransferase | Involved in phospholipid remodeling |
| LPEAT2 | Lysophosphatidylethanolamine acyltransferase | Involved in phospholipid remodeling |
| PLA2G4A | Phospholipase A2 | Catalyzes deacylation of phospholipids |
| PLA2G6 | Phospholipase A2 | Catalyzes deacylation of phospholipids |
| GPAT1 | Glycerol-3-phosphate acyltransferase | Involved in initial acylation steps |
How Is acylglycerol acyl-chain remodeling Regulated?
Acylglycerol acyl-chain remodeling is regulated at multiple levels. In plants, membrane lipid remodeling is induced by environmental stresses such as cold and drought. In mammals, DGAT-mediated lipid droplet biogenesis is regulated by nutrient availability and influences ferroptosis sensitivity. The activity of remodeling enzymes can be modulated by their substrate availability and by post-translational modifications, though specific regulatory mechanisms require further study.
acylglycerol acyl-chain remodeling and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LPLAT10/LPEAT2 | X-linked adrenoleukodystrophy | Knockout or point-mutation cell models to study C26:0 phosphatidylcholine synthesis |
| DGAT1 | Ferroptosis sensitivity, metabolic disorders | Overexpression and knockout models to assess lipid droplet biogenesis |
| DGAT2 | Ferroptosis sensitivity, metabolic disorders | Overexpression and knockout models to assess lipid droplet biogenesis |
| LYCAT | Membrane trafficking defects | Knockout models to study phosphoinositide remodeling |
| DDHD2 | Neurodegeneration, lipid metabolism | Knockout and knock-in models to study triglyceride remodeling |
X-Linked Adrenoleukodystrophy (X-ALD)
X-ALD is associated with the accumulation of very-long-chain fatty acids, particularly C26:0. LPLAT10/LPEAT2 synthesizes phosphatidylcholine with C26:0 moiety, which is a precursor of a diagnostic marker for X-ALD. This links acyl-chain remodeling to the pathophysiology of the disease.
Ferroptosis and Cancer
DGAT-mediated lipid droplet biogenesis and acyl-chain remodeling regulate ferroptosis sensitivity. Ferroptosis is a form of regulated cell death implicated in cancer and neurodegeneration, suggesting that targeting remodeling enzymes could modulate cell death pathways.
Metabolic Disorders
Diet-induced obesity modulates the close-packing of triacylglycerols in lipid droplets of adipose tissue, indicating that acyl-chain remodeling is affected in metabolic disorders. This may contribute to altered lipid storage and insulin resistance.
From acylglycerol acyl-chain remodeling-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does DDHD2 lipase activity contribute to triglyceride remodeling? | Point mutation of catalytic residues in DDHD2 |
| What is the role of LYCAT in phosphoinositide remodeling? | Knockout of LYCAT in cell lines |
| How does LPLAT10/LPEAT2 affect C26:0 phosphatidylcholine levels? | Overexpression and knockout models |
| Does DGAT1/2-mediated remodeling influence ferroptosis? | Knockout and overexpression in cancer cell lines |
| How does diet-induced obesity alter acyl-chain packing? | Knock-in of tagged DGAT for imaging in adipose tissue |
| What is the flux of acyl chains during stress? | Stable isotopic labeling in microalgae |
How to Study the acylglycerol acyl-chain remodeling Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics (LC-MS/MS) | Acyl chain composition of acylglycerols | Profiling remodeling products in cells |
| Stable isotopic labeling | Carbon and acyl chain flux | Tracking remodeling under stress |
| Fluorescence microscopy | Lipid droplet dynamics and localization | Visualizing remodeling in live cells |
| Enzymatic activity assay | Lipase and acyltransferase activity | Characterizing enzyme function |
| Western blotting | Protein expression levels | Assessing enzyme regulation |
| qPCR | mRNA expression of remodeling genes | Screening for transcriptional changes |
| CRISPR screening | Gene essentiality for remodeling | Identifying novel regulators |
| Co-immunoprecipitation | Protein-protein interactions | Mapping remodeling complexes |
Lipidomics and Mass Spectrometry
Mass spectrometry-based lipidomics allows comprehensive profiling of acylglycerol species and their acyl chain compositions. This method can quantify changes in remodeling products and identify specific fatty acid moieties.
Stable Isotopic Labeling
Stable isotopic labeling with 13C or deuterium tracks carbon and acyl chain flux through remodeling pathways. This approach has been used to study stress-induced triglyceride accumulation in microalgae.
Fluorescence Microscopy and Imaging
Fluorescently tagged lipid droplets and acyl chain analogs enable visualization of remodeling dynamics in live cells. This helps assess lipid droplet biogenesis and trafficking.
Enzymatic Activity Assays
In vitro assays using recombinant enzymes and synthetic substrates measure lipase and acyltransferase activities. These assays have characterized DDHD2's dual lipase and transacylase functions.
How CRISPR Can Be Used to Study GO:0036155 acylglycerol acyl-chain remodeling
Knockout
CRISPR knockout of genes such as DDHD2, LYCAT, or DGAT1/2 can abolish specific remodeling steps, revealing their contribution to lipid metabolism and disease. For example, LYCAT knockout alters phosphoinositide composition.
Point Mutation
Introducing point mutations in catalytic residues of remodeling enzymes, such as DDHD2, can dissect their lipase versus transacylase activities without affecting protein stability.
Knock-in
Knock-in of tagged versions of remodeling enzymes (e.g., GFP-DGAT1) allows real-time imaging of lipid droplet dynamics and protein localization.
Overexpression
Overexpression of LPLAT10/LPEAT2 or DGAT enzymes can increase specific acyl chain species and lipid droplet formation, providing gain-of-function models for studying remodeling.
How EDITGENE Supports acylglycerol acyl-chain remodeling Research
Researchers studying acylglycerol acyl-chain remodeling-related genes often need to determine whether a candidate gene is causally involved in lipid metabolism, membrane dynamics, or disease. EDITGENE provides comprehensive CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for acylglycerol acyl-chain remodeling research.
Frequently Asked Questions About acylglycerol acyl-chain remodeling
What is acylglycerol acyl-chain remodeling?
Acylglycerol acyl-chain remodeling (GO:0036155) is the process of modifying the fatty acid chains of acylglycerols through sequential deacylation and re-acylation, generating molecules with different acyl chain compositions.
What genes are involved in acylglycerol acyl-chain remodeling?
Key genes include DDHD2, LYCAT, LPLAT10/LPEAT2, DGAT1, DGAT2, and various lipases and acyltransferases.
What is the role of DDHD2 in acyl-chain remodeling?
DDHD2 possesses both lipase and transacylase activities that remodel triglyceride acyl chains.
How does LYCAT control phosphoinositides?
LYCAT is an acyltransferase that controls specific phosphoinositides and related membrane traffic.
What diseases are linked to acylglycerol acyl-chain remodeling?
Diseases include X-linked adrenoleukodystrophy, ferroptosis-related conditions, and metabolic disorders.
How can I study acylglycerol acyl-chain remodeling in the lab?
Methods include lipidomics, stable isotopic labeling, fluorescence microscopy, and enzymatic assays.
What is the connection between acyl-chain remodeling and ferroptosis?
DGAT-mediated lipid droplet biogenesis and acyl-chain remodeling regulate ferroptosis sensitivity.
Which enzymes synthesize C26:0 phosphatidylcholine?
LPLAT10/LPEAT2 synthesizes phosphatidylcholine with C26:0 moiety, a precursor of a diagnostic marker for X-ALD.
How does diet-induced obesity affect acyl-chain remodeling?
Diet-induced obesity modulates close-packing of triacylglycerols in lipid droplets of adipose tissue.
What CRISPR models are available for studying acyl-chain remodeling?
EDITGENE offers knockout, point mutation, knock-in, overexpression, and library screening services for genes involved in this process.
Conclusion
Acylglycerol acyl-chain remodeling (GO:0036155) is a fundamental biological process that adjusts the fatty acid composition of acylglycerols, impacting membrane function, lipid storage, and cell death pathways. Key enzymes such as DDHD2, LYCAT, and LPLAT10/LPEAT2 have been characterized, revealing their roles in health and disease. Continued research using CRISPR models and advanced lipidomics will further elucidate the regulatory mechanisms and therapeutic potential of targeting this pathway.
References
- 1. Yu L et al.. 2021. Mechanisms and functions of membrane lipid remodeling in plants.. Plant J 107(1):37-53 PMID: 33853198
- 2. Wu L et al.. 2025. DDHD2 possesses both lipase and transacylase capacities that remodel triglyceride acyl chains.. Proc Natl Acad Sci U S A 122(47):e2500527122 PMID: 41264248
- 3. Vanni S et al.. 2019. Structure and Dynamics of the Acyl Chains in the Membrane Trafficking and Enzymatic Processing of Lipids.. Acc Chem Res 52(11):3087-3096 PMID: 31364837
- 4. Kump A et al.. 2026. Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.. FEBS J 293(15):4508-4532 PMID: 41729026
- 5. Allen JW et al.. 2017. Carbon and Acyl Chain Flux during Stress-induced Triglyceride Accumulation by Stable Isotopic Labeling of the Polar Microalga Coccomyxa subellipsoidea C169.. J Biol Chem 292(1):361-374 PMID: 27903654
- 6. Hama K et al.. 2026. Phosphatidylcholine with C26:0 moiety, a precursor of a diagnostic marker for X-ALD, is synthesized by LPLAT10/LPEAT2.. J Lipid Res 67(2):100973 PMID: 41478358
- 7. Ko K et al.. 2024. Diet-Induced Obesity Modulates Close-Packing of Triacylglycerols in Lipid Droplets of Adipose Tissue.. J Am Chem Soc 146(50):34796-34810 PMID: 39644234
- 8. Bone LN et al.. 2017. The acyltransferase LYCAT controls specific phosphoinositides and related membrane traffic.. Mol Biol Cell 28(1):161-172 PMID: 28035047
