GO:0071617 lysophospholipid acyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071617 lysophospholipid acyltransferase activity is a molecular function defined as the catalysis of acyl group transfer from an acyl-CoA donor to a lysophospholipid acceptor, a reaction central to phospholipid remodeling.
• This activity is executed by the LPLAT/LPCAT enzyme family, including LPCAT1, LPCAT2, LPCAT3, LPCAT4, MBOAT1, MBOAT2, and LPLAT9, which determine membrane phospholipid composition [1,2].
• Lysophospholipid acyltransferase activity controls membrane fluidity, curvature, and signaling lipid availability, influencing ferroptosis sensitivity, inflammation, and metabolic homeostasis [1,5,6].
• Dysregulated lysophospholipid acyltransferase activity is implicated in colorectal cancer, nonalcoholic steatohepatitis, emphysema, and adipose storage capacity [3,4,6,7,8].
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential to establish causal roles of individual LPLAT enzymes in disease and to validate drug targets [3,5,7].
• Studying GO:0071617 requires integrated lipidomics, transcriptomics, and functional assays such as ferroptosis induction and platelet-activating factor measurement [5,7].
Description
Lysophospholipid acyltransferase activity (GO:0071617) is a molecular function that catalyzes the transfer of an acyl group from an acyl-CoA thioester to a lysophospholipid acceptor, thereby regenerating a diacyl phospholipid. This reaction, often called the Lands cycle, is a major determinant of membrane phospholipid diversity and asymmetry in eukaryotic cells [1,2]. Because phospholipids are not merely structural barriers but also reservoirs of signaling molecules, the enzymes that carry out this activity sit at the crossroads of membrane biology, inflammation, and metabolism [1,2]. Researchers study GO:0071617 to understand how cells maintain membrane homeostasis under stress, how lipid remodeling contributes to diseases such as cancer and steatohepatitis, and how this activity can be targeted therapeutically [3,4,5,6]. The reaction is also critical for the incorporation of polyunsaturated fatty acids into membrane phospholipids, a process that influences ferroptosis susceptibility and immune signaling [1,5]. Given its broad physiological impact, lysophospholipid acyltransferase activity is a compelling entry point for functional genomics and drug discovery.
lysophospholipid acyltransferase activity At A Glance
| GO ID | GO:0071617 |
|---|---|
| GO term | lysophospholipid acyltransferase activity |
| Ontology | molecular_function |
| Synonym | (none) |
| Major function | Catalysis of acyl group transfer from acyl-CoA to a lysophospholipid |
| Reaction direction | Acyl-CoA + lysophospholipid -> CoA + phospholipid |
| Substrates | Acyl-CoA donors and lysophospholipid acceptors |
| Representative enzymes | LPCAT1, LPCAT2, LPCAT3, LPCAT4, MBOAT1, MBOAT2, LPLAT9 |
| Biological context | Phospholipid remodeling, membrane homeostasis, ferroptosis, inflammation |
What Is GO:0071617?
According to the Gene Ontology, GO:0071617 (lysophospholipid acyltransferase activity) is defined as the catalysis of the transfer of acyl groups from an acyl-CoA to a lysophospholipid. In other words, the enzyme takes a fatty acid carried by coenzyme A and attaches it to a lysophospholipid, which is a phospholipid missing one acyl chain, to produce a fully acylated phospholipid. This activity is a key step in phospholipid remodeling and is distinct from de novo phospholipid synthesis because it acts on pre-existing lysophospholipids.
Why Is lysophospholipid acyltransferase activity Important in Cell Biology?
Lysophospholipid acyltransferase activity is fundamentally important because it determines the acyl chain composition of membrane phospholipids, which in turn controls membrane fluidity, curvature, protein-lipid interactions, and the availability of lipid mediators [1,2]. By shaping the membrane lipidome, this activity influences diverse processes such as ferroptosis, inflammatory signaling, and metabolic adaptation [1,5,6]. Consequently, enzymes with this activity are implicated in cancer progression, liver disease, lung disease, and adipose tissue expansion, making them attractive targets for therapeutic intervention and biomarkers [3,4,7,8].
• Controls membrane phospholipid remodeling and acyl chain saturation, affecting membrane biophysical properties.
• Regulates ferroptosis sensitivity by determining the abundance of polyunsaturated phospholipids [1,5].
• Modulates inflammatory signaling through the production or removal of lysophospholipid mediators.
• Influences cancer progression, as shown for LPCAT2 in colorectal cancer.
• Contributes to nonalcoholic steatohepatitis progression via mitochondrial homeostasis.
• Promotes emphysema formation through platelet-activating factor regulation by LPLAT9.
• Affects systemic metabolic health and adipose storage capacity.
• Provides potential drug targets for immunotherapy enhancement.
• Serves as a node for understanding SCAP/SREBP-related liver injury.
• Enables functional genomics studies of lipid metabolism using CRISPR screens [3,5].
Molecular Mechanism of lysophospholipid acyltransferase activity
Substrate recognition and binding
In simple terms: The enzyme grabs a fatty acid carrier and a partially built phospholipid.
Lysophospholipid acyltransferases bind two substrates: an acyl-CoA thioester and a lysophospholipid. The acyl-CoA provides the fatty acid, while the lysophospholipid provides the glycerol backbone with a free hydroxyl group. Specificity for different acyl-CoA species and lysophospholipid head groups varies among family members, contributing to the diversity of phospholipid species in membranes [1,2].
Catalytic transfer of the acyl group
In simple terms: The enzyme moves the fatty acid from CoA onto the lysophospholipid.
The catalytic mechanism involves nucleophilic attack of the lysophospholipid hydroxyl on the acyl-CoA thioester, forming a tetrahedral intermediate and releasing coenzyme A. This results in a diacyl phospholipid. The reaction is reversible in principle but is driven forward by substrate availability and product removal. Conserved histidine and aspartate residues in the active site are thought to facilitate catalysis in many LPLAT enzymes.
Membrane insertion and topology
In simple terms: The enzyme works inside the membrane where lipids are made.
Most lysophospholipid acyltransferases are integral membrane proteins localized to the endoplasmic reticulum and, in some cases, lipid droplets or mitochondria-associated membranes. Their active sites face the cytosol or the membrane bilayer, allowing access to acyl-CoA pools and lysophospholipids generated by phospholipase A2 or other lipases [1,2].
Regulation by substrate availability and signaling
In simple terms: The enzyme's activity depends on how much starting material is around and on cellular signals.
The activity of lysophospholipid acyltransferases is regulated by the availability of acyl-CoA and lysophospholipids, which fluctuate with dietary lipid intake and metabolic state. Inflammatory signals can increase lysophospholipid production, thereby driving acyltransferase activity. Additionally, transcriptional regulation by SREBP and other lipid-sensing pathways modulates enzyme levels, as suggested by studies on SCAP/SREBP in liver injury.
Role in ferroptosis and phospholipid peroxidation
In simple terms: The enzyme can make membranes more or less vulnerable to a type of cell death called ferroptosis.
By incorporating polyunsaturated fatty acids into phospholipids, lysophospholipid acyltransferase activity generates substrates for lipid peroxidation, which is the hallmark of ferroptosis. LPCAT3 is a key enzyme in this context, and its activity can be modulated to enhance ferroptosis in tumors, as shown for mefloquine-enhanced immunotherapy. Conversely, limiting this activity can protect cells from ferroptotic death.
Key Genes Involved in GO:0071617 lysophospholipid acyltransferase activity
The following genes encode enzymes with lysophospholipid acyltransferase activity or are directly involved in the reaction, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| LPCAT1 | Lysophosphatidylcholine acyltransferase 1; remodels phosphatidylcholine | Studied in cancer and lipid metabolism [1,2] |
| LPCAT2 | Lysophosphatidylcholine acyltransferase 2; also acetyltransferase | Inhibits colorectal cancer progression via PRMT1/SLC7A11 axis |
| LPCAT3 | Lysophosphatidylcholine acyltransferase 3; incorporates PUFA into phospholipids | Key regulator of ferroptosis and immunotherapy response [1,5] |
| LPCAT4 | Lysophosphatidylcholine acyltransferase 4; broad substrate specificity | Implicated in phospholipid remodeling |
| MBOAT1 | Membrane-bound O-acyltransferase 1; lysophospholipid acyltransferase | Contributes to membrane lipid diversity |
| MBOAT2 | Membrane-bound O-acyltransferase 2; lysophospholipid acyltransferase | Involved in phospholipid remodeling |
| LPLAT9 | Lysophospholipid acyltransferase 9; also known as LPCAT2 in some contexts | Promotes emphysema via platelet-activating factor |
| AGPAT1 | Acylglycerophosphate acyltransferase 1; related acyltransferase | Participates in glycerophospholipid synthesis |
| AGPAT2 | Acylglycerophosphate acyltransferase 2 | Linked to lipodystrophy and lipid metabolism |
| GPAT1 | Glycerol-3-phosphate acyltransferase 1 | Involved in de novo glycerolipid synthesis |
| GPAT2 | Glycerol-3-phosphate acyltransferase 2 | Testis-specific acyltransferase |
| PLA2G4A | Phospholipase A2 group IVA; generates lysophospholipids | Provides substrate for acyltransferase activity |
| PLA2G6 | Phospholipase A2 group VI; calcium-independent | Generates lysophospholipids for remodeling |
| SREBF1 | Sterol regulatory element-binding transcription factor 1 | Regulates lipogenic genes including acyltransferases |
| SREBF2 | Sterol regulatory element-binding transcription factor 2 | Controls cholesterol and lipid homeostasis |
| SCAP | SREBP cleavage-activating protein | Regulates SREBP processing; affects liver injury |
| PRMT1 | Protein arginine methyltransferase 1 | Modulates LPCAT2 effects in colorectal cancer |
| SLC7A11 | Cystine/glutamate antiporter | Linked to LPCAT2-mediated ferroptosis resistance |
How Is lysophospholipid acyltransferase activity Regulated?
Lysophospholipid acyltransferase activity is regulated at multiple levels. Transcriptionally, the genes encoding these enzymes are influenced by lipid-sensing transcription factors such as SREBP, which respond to cellular sterol and fatty acid levels. Post-translationally, enzyme activity can be modulated by phosphorylation and other modifications, although specific sites are not fully defined for all family members. Substrate availability is a major determinant: acyl-CoA pools depend on dietary fatty acids and metabolic state, while lysophospholipid levels are controlled by phospholipase A2 activity and inflammatory signaling [2,8]. In disease contexts, such as nonalcoholic steatohepatitis, altered expression of remodeling enzymes contributes to mitochondrial dysfunction and disease progression. Additionally, the activity can be influenced by the membrane environment itself, including cholesterol content and phospholipid saturation.
lysophospholipid acyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LPCAT2 | Colorectal cancer progression | Knockout and overexpression in HCT116 or SW480 cells |
| LPCAT3 | Ferroptosis and immunotherapy response | Knockout in B16F10 melanoma or MC38 colon cancer cells |
| LPLAT9 | Emphysema via platelet-activating factor | Knockout mice exposed to cigarette smoke |
| MBOAT1/2 | Nonalcoholic steatohepatitis | Liver-specific knockout in mice fed high-fat diet |
| LPCAT1 | Adipose storage capacity | Adipose-specific overexpression in mice |
Cancer and ferroptosis
Lysophospholipid acyltransferase activity is increasingly linked to cancer biology through its role in ferroptosis. LPCAT3 incorporates polyunsaturated fatty acids into phospholipids, making cells susceptible to lipid peroxidation and ferroptotic death. Enhancing this activity with compounds like mefloquine can boost anti-PD-1 immunotherapy efficacy via IFN-gamma-STAT1-IRF1 signaling. In colorectal cancer, LPCAT2 inhibits progression through the PRMT1/SLC7A11 axis, highlighting context-dependent roles. These findings suggest that modulating acyltransferase activity could be a therapeutic strategy in oncology.
Liver disease and metabolic dysfunction
In nonalcoholic steatohepatitis (NASH), membrane phospholipid remodeling modulates disease progression by regulating mitochondrial homeostasis. Inhibiting SCAP/SREBP, which controls lipogenic gene expression including acyltransferases, exacerbates liver injury and carcinogenesis in murine NASH, indicating that balanced acyltransferase activity is protective. Dietary control of adipose storage capacity also involves membrane lipid remodeling, linking acyltransferase activity to systemic metabolic health.
Respiratory and inflammatory diseases
LPLAT9 promotes emphysema formation via platelet-activating factor, demonstrating that lysophospholipid acyltransferase activity can drive inflammatory lung disease. Lysophosphatidylcholine metabolism, which is directly affected by acyltransferase activity, is reviewed as a contributor to human inflammatory diseases. These connections position acyltransferases as potential targets for anti-inflammatory therapies in respiratory conditions.
From lysophospholipid acyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is LPCAT3 required for ferroptosis? | CRISPR knockout in cancer cell lines followed by ferroptosis induction |
| Does LPCAT2 mutation affect colorectal cancer growth? | Point mutation knock-in of catalytic dead variant in HCT116 cells |
| Can LPLAT9 overexpression induce emphysema? | Transgenic overexpression in mouse lung epithelium |
| What is the role of MBOAT1 in NASH? | Liver-specific knockout mice fed a NASH diet |
| How does LPCAT1 affect adipose tissue? | Adipose-specific knockout or overexpression in mice |
| Does SCAP/SREBP regulate acyltransferase genes? | Knockout of SCAP in hepatocytes and lipidomics |
How to Study the lysophospholipid acyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics (LC-MS/MS) | Phospholipid species and acyl chain composition | Quantifying remodeling in knockout cells [1,6] |
| CRISPR knockout screen | Genes required for a phenotype | Identifying ferroptosis regulators |
| RNA-seq | Transcriptional changes | Assessing SREBP target genes |
| Proteomics | Protein abundance and modifications | Validating enzyme expression |
| In vitro acyltransferase assay | Enzymatic activity | Testing substrate specificity and inhibitors |
| Platelet-activating factor measurement | PAF levels | Linking LPLAT9 to emphysema |
| Ferroptosis induction assay | Cell death and lipid peroxidation | Evaluating LPCAT3 function |
Lipidomics and mass spectrometry
Mass spectrometry-based lipidomics is the primary method to measure changes in phospholipid species resulting from lysophospholipid acyltransferase activity. By comparing wild-type and knockout cells, researchers can quantify shifts in acyl chain composition and identify specific substrates and products [1,6]. This approach is essential for linking enzyme activity to membrane remodeling and disease phenotypes.
CRISPR screens and functional genomics
Genome-wide CRISPR knockout screens can identify genes required for lysophospholipid acyltransferase activity-dependent processes, such as ferroptosis sensitivity or cancer cell growth [3,5]. These screens often use reporters of lipid peroxidation or cell viability to uncover modifiers. Follow-up validation with individual knockouts confirms causality.
Transcriptomics and proteomics
RNA sequencing and quantitative proteomics reveal how expression of LPLAT family members changes across conditions and how their activity affects downstream gene expression programs [4,6]. Integrating these datasets with lipidomics provides a systems-level view of acyltransferase function in health and disease.
Enzymatic activity assays
In vitro acyltransferase assays using fluorescent or radiolabeled acyl-CoA and lysophospholipid substrates allow direct measurement of catalytic activity. These assays can be performed with recombinant enzymes or membrane fractions and are useful for testing inhibitors or mutants [1,2].
How CRISPR Can Be Used to Study GO:0071617 lysophospholipid acyltransferase activity
Knockout
CRISPR knockout of genes encoding lysophospholipid acyltransferases, such as LPCAT3 or LPCAT2, is used to abolish enzyme activity and assess consequences on phospholipid composition, ferroptosis, and cancer cell growth [3,5]. Knockout models are essential for establishing loss-of-function phenotypes and for validating drug targets.
Point Mutation
Point mutations that inactivate the catalytic site or alter substrate specificity can be introduced via CRISPR to dissect the enzymatic versus non-enzymatic functions of acyltransferases. For example, mutating conserved histidine residues can abolish acyltransferase activity while preserving protein interactions.
Knock-in
Knock-in of epitope tags or fluorescent reporters allows visualization and purification of endogenous acyltransferase enzymes. This approach is valuable for studying subcellular localization, protein interactions, and dynamics in live cells.
Overexpression
CRISPR activation or cDNA overexpression of LPLAT genes can drive increased acyltransferase activity, enabling gain-of-function studies. Overexpression of LPCAT1 or LPLAT9 has been used to model adipose expansion and emphysema, respectively [7,8].
How EDITGENE Supports lysophospholipid acyltransferase activity Research
Researchers studying lysophospholipid acyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in a specific phenotype, such as ferroptosis sensitivity, lipid remodeling, or disease progression. Establishing causality requires precise genetic manipulation, and CRISPR-based models are the gold standard for this purpose.
Contact EDITGENE today to design your custom CRISPR model for lysophospholipid acyltransferase activity research.
Frequently Asked Questions About lysophospholipid acyltransferase activity
What is lysophospholipid acyltransferase activity?
It is a molecular function defined by GO:0071617, catalyzing the transfer of an acyl group from acyl-CoA to a lysophospholipid, a key step in phospholipid remodeling.
What genes are involved in lysophospholipid acyltransferase activity?
Major genes include LPCAT1, LPCAT2, LPCAT3, LPCAT4, MBOAT1, MBOAT2, and LPLAT9, among others [1,2,7].
What is the GO ID for lysophospholipid acyltransferase activity?
The Gene Ontology ID is GO:0071617.
How is lysophospholipid acyltransferase activity related to ferroptosis?
By incorporating polyunsaturated fatty acids into phospholipids, this activity generates substrates for lipid peroxidation, which drives ferroptosis [1,5].
Which diseases are associated with lysophospholipid acyltransferase activity?
It is implicated in colorectal cancer, nonalcoholic steatohepatitis, emphysema, and metabolic disorders [3,4,6,7,8].
What is the role of LPCAT3 in cancer immunotherapy?
LPCAT3-mediated ferroptosis can enhance anti-PD-1 immunotherapy efficacy via IFN-gamma-STAT1-IRF1 signaling.
How can I study lysophospholipid acyltransferase activity in the lab?
Common methods include lipidomics, CRISPR knockout screens, in vitro enzymatic assays, and ferroptosis induction assays [1,5].
What are the substrates of lysophospholipid acyltransferase?
The substrates are an acyl-CoA donor and a lysophospholipid acceptor.
Is lysophospholipid acyltransferase activity reversible?
The reaction is reversible in principle but is driven forward by substrate availability and product removal.
What model systems are used to study lysophospholipid acyltransferase activity?
Cell lines with CRISPR knockouts, transgenic mice, and in vitro enzyme assays are commonly used [3,5,7].
Conclusion
Lysophospholipid acyltransferase activity (GO:0071617) is a central molecular function in phospholipid remodeling, with far-reaching implications for membrane biology, ferroptosis, inflammation, and metabolic disease. The LPLAT enzyme family, including LPCAT1-4, MBOAT1/2, and LPLAT9, executes this activity and has been linked to cancer, liver disease, emphysema, and adipose storage capacity [1,3,4,6,7,8]. Understanding the precise roles of these enzymes requires robust genetic models, and CRISPR-based knockout, point mutation, knock-in, and overexpression approaches are indispensable for causal inference [3,5]. As research advances, targeting lysophospholipid acyltransferase activity may offer new therapeutic opportunities in oncology, hepatology, and inflammatory diseases.
References
- 1. Wang B et al.. 2019. Phospholipid Remodeling in Physiology and Disease.. Annu Rev Physiol 81:165-188 PMID: 30379616
- 2. Law SH et al.. 2019. An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases.. Int J Mol Sci 20(5) PMID: 30845751
- 3. Cao N et al.. 2024. LPCAT2 inhibits colorectal cancer progression via the PRMT1/SLC7A11 axis.. Oncogene 43(22):1714-1725 PMID: 38605214
- 4. Kawamura S et al.. 2022. Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis.. J Clin Invest 132(11) PMID: 35380992
- 5. Tao Q et al.. 2024. Mefloquine enhances the efficacy of anti-PD-1 immunotherapy via IFN-γ-STAT1-IRF1-LPCAT3-induced ferroptosis in tumors.. J Immunother Cancer 12(3) PMID: 38471712
- 6. Tian Y et al.. 2024. Membrane phospholipid remodeling modulates nonalcoholic steatohepatitis progression by regulating mitochondrial homeostasis.. Hepatology 79(4):882-897 PMID: 36999536
- 7. Murano H et al.. 2024. Lysophospholipid Acyltransferase 9 Promotes Emphysema Formation via Platelet-activating Factor.. Am J Respir Cell Mol Biol 70(6):482-492 PMID: 38377392
- 8. Tol MJ et al.. 2025. Dietary control of peripheral adipose storage capacity through membrane lipid remodelling.. Nat Metab 7(7):1424-1442 PMID: 40579620
