GO:0000062 fatty-acyl-CoA binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0000062 fatty-acyl-CoA binding describes the molecular function of reversibly binding fatty-acyl-CoA, a coenzyme A thioester of a fatty acid.
• Acyl-CoA-binding proteins (ACBPs) are the archetypal carriers for this function and shuttle fatty-acyl-CoA between membranes and enzymes.
• TANGO2 is a recently validated acyl-CoA binding protein whose loss impairs mitochondrial fatty-acid handling.
• ACBP/DBI fuels gliomagenesis, linking fatty-acyl-CoA binding to cancer metabolism.
• Fatty-acyl-CoA binding is essential for mitochondrial beta-oxidation of saturated fatty acids.
• Model systems from Drosophila ACBP6 to Aspergillus AcbdA reveal conserved roles in nutrient adaptation and peroxisome biology.
Description
GO:0000062 fatty-acyl-CoA binding is a molecular function term that captures the reversible, non-covalent interaction between a protein and a fatty-acyl-CoA molecule, which is a coenzyme A derivative in which the sulfhydryl group is in thiolester linkage with a fatty acyl group. This binding event is the first committed step in many lipid-handling pathways because it solubilizes otherwise amphipathic acyl chains and presents them to enzymes or membranes. The term is distinct from fatty acid binding, although the two functions are often compared because both manage hydrophobic ligands in aqueous compartments. Researchers study fatty-acyl-CoA binding because it sits at the crossroads of energy metabolism, membrane trafficking, and signaling. Defects in acyl-CoA-binding proteins are increasingly linked to human disease, including metabolic and neurological phenotypes. The function is also central to mitochondrial beta-oxidation, where saturated fatty acids are oxidized to acetyl-CoA. Short- and medium-chain fatty acids add another layer of complexity because their cellular handling depends on acyl-CoA binding and transport. In this article we integrate the QuickGO definition with verified PubMed literature to explain the mechanism, genes, and experimental models for GO:0000062.
fatty-acyl-CoA binding At A Glance
| GO ID | GO:0000062 |
|---|---|
| GO term | fatty-acyl-CoA binding |
| Ontology | molecular_function |
| Synonym | fatty-acyl binding; fatty-acyl-coenzyme A binding |
| Definition | Binding to a fatty-acyl-CoA, any derivative of coenzyme A in which the sulfhydryl group is in thiolester linkage with a fatty acyl group. |
| Major function | Reversible binding and presentation of fatty-acyl-CoA for metabolism, transport, or signaling |
| Representative proteins | ACBP/DBI, TANGO2, ACBP6, AcbdA |
| Related process | Mitochondrial beta-oxidation of saturated fatty acids |
| Disease relevance | Cancer metabolism and metabolic/neurological phenotypes |
What Is GO:0000062?
In our own words, fatty-acyl-CoA binding (GO:0000062) is the molecular function of selectively and reversibly binding a fatty-acyl-CoA, meaning any derivative of coenzyme A in which the sulfhydryl group is in thiolester linkage with a fatty acyl group. This function is mediated by defined binding pockets or amphipathic helices that accommodate the acyl chain and the CoA moiety, and it does not necessarily imply catalysis. It is a binding term, not an enzymatic activity term, although binding often precedes or regulates catalysis.
Why Is fatty-acyl-CoA binding Important in Cell Biology?
Fatty-acyl-CoA binding is important because it controls the bioavailability of acyl-CoA, a central metabolite that feeds beta-oxidation, lipid synthesis, and protein acylation. Without proper binding, acyl-CoA can disrupt membranes or inhibit unrelated enzymes, so carrier proteins such as ACBP/DBI maintain a usable pool. The function is also emerging as a therapeutic node in cancer, where ACBP supports gliomagenesis, and in inherited disorders such as TANGO2-related disease. Because fatty-acyl-CoA binding influences energy metabolism and membrane trafficking, it is relevant to obesity, neurodegeneration, and rare metabolic disease research.
• Provides soluble acyl-CoA pools for mitochondrial beta-oxidation.
• Prevents membrane perturbation by amphipathic acyl-CoA species.
• Supports cancer metabolism, including gliomagenesis.
• Underlies TANGO2-related metabolic and neurological disease.
• Enables peroxisome hitchhiking on early endosomes in fungi.
• Mediates nutrient adaptation and tissue plasticity in Drosophila.
• Connects short- and medium-chain fatty acid handling to cellular energy state.
• Serves as a target for lipid metabolism and acylation studies.
• Links acyl-CoA availability to protein palmitoylation by membrane palmitoyltransferases.
• Offers a druggable interface for metabolic and oncogenic pathways.
Molecular Mechanism of fatty-acyl-CoA binding
Ligand recognition and binding pocket
In simple terms: The protein has a pocket that fits the fatty acyl chain and the CoA head.
Fatty-acyl-CoA binding proteins such as ACBP/DBI use a conserved hydrophobic pocket to engulf the acyl chain while polar residues engage the CoA moiety. This bivalent recognition is also seen in integral membrane palmitoyltransferases, which bind fatty acyl-CoA in a two-part mode. The binding is non-covalent and reversible, allowing transfer to downstream enzymes.
Acyl chain length and saturation
In simple terms: Different proteins prefer different fatty acid lengths.
ACBP/DBI binds medium- and long-chain acyl-CoA esters with high affinity, whereas short- and medium-chain fatty acids have distinct cellular handling. TANGO2 binds acyl-CoA and its loss alters mitochondrial fatty-acid metabolism. The specificity of binding influences which pathways are fed.
Membrane interaction and transfer
In simple terms: The carrier hands the fatty acyl-CoA to membranes or enzymes.
ACBP/DBI can interact with membranes and donate acyl-CoA to enzymes or transport systems. In Aspergillus nidulans, AcbdA is required for peroxisome hitchhiking on early endosomes, showing that acyl-CoA binding proteins can couple lipid cargo to organelle motility. This transfer step is critical for beta-oxidation and lipid remodeling.
Regulation by nutrient state
In simple terms: The cell adjusts acyl-CoA binding when nutrients change.
In Drosophila, ACBP6 shapes tissue plasticity during nutrient adaptation, indicating that fatty-acyl-CoA binding is tuned to metabolic state. Short- and medium-chain fatty acids also signal cellular energy status. These observations place GO:0000062 under metabolic regulation.
Coupling to acylation and signaling
In simple terms: Bound acyl-CoA can be used to modify proteins.
Human integral membrane palmitoyltransferases bind fatty acyl-CoA for protein palmitoylation, linking GO:0000062 to signaling. ACBP/DBI supports gliomagenesis, suggesting that acyl-CoA binding can feed oncogenic lipid signaling. Thus the function is not only metabolic but also regulatory.
Key Genes Involved in GO:0000062 fatty-acyl-CoA binding
The following genes and proteins represent the main experimental handles for studying fatty-acyl-CoA binding (GO:0000062).
| Gene | Major Role | Research Relevance |
|---|---|---|
| DBI (ACBP) | Archetypal acyl-CoA binding protein | Metabolic and cancer studies |
| TANGO2 | Acyl-CoA binding protein in mitochondria | TANGO2-related disease models |
| ACBP6 | Drosophila acyl-CoA binding protein | Nutrient adaptation and tissue plasticity |
| AcbdA | Aspergillus acyl-CoA binding protein | Peroxisome hitchhiking on endosomes |
| ZDHHC family | Integral membrane palmitoyltransferases | Bivalent fatty acyl-CoA recognition |
| CPT1A | Mitochondrial beta-oxidation entry | Fatty acid oxidation research |
| ACADM | Acyl-CoA dehydrogenase | Beta-oxidation studies |
| HADHA | Trifunctional protein subunit | Mitochondrial fatty acid oxidation |
| ACOX1 | Peroxisomal acyl-CoA oxidase | Peroxisome biology |
| FABP3 | Fatty acid binding protein | Comparison with ACBP |
| FABP4 | Fatty acid binding protein | Lipid metabolism |
| SLC25A20 | Carnitine-acylcarnitine translocase | Beta-oxidation transport |
| ETFA | Electron transfer flavoprotein | Mitochondrial oxidation |
| ETFB | Electron transfer flavoprotein | Mitochondrial oxidation |
| ACAA2 | Thiolase in beta-oxidation | Fatty acid oxidation |
| PEX5 | Peroxisomal import receptor | Peroxisome hitchhiking |
| PEX14 | Peroxisomal membrane protein | Peroxisome motility |
How Is fatty-acyl-CoA binding Regulated?
Fatty-acyl-CoA binding is regulated by nutrient availability and metabolic state. In Drosophila, ACBP6 shapes tissue plasticity during nutrient adaptation, showing that expression or activity of acyl-CoA binding proteins responds to diet. Short- and medium-chain fatty acids influence cellular energy metabolism and can alter the demand for acyl-CoA carriers. In cancer, ACBP/DBI supports gliomagenesis, implying that oncogenic signaling can upregulate or depend on this function. Mitochondrial beta-oxidation flux itself is a regulatory input because acyl-CoA binding feeds this pathway. Finally, membrane palmitoyltransferases couple fatty acyl-CoA binding to protein acylation, adding a signaling layer.
fatty-acyl-CoA binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| TANGO2 | TANGO2-related metabolic and neurological disease | Knockout and rescue in cell lines |
| DBI (ACBP) | Gliomagenesis and cancer metabolism | Overexpression and knockout in glioma models |
| ACBP6 | Nutrient adaptation phenotypes | Drosophila knockout and overexpression |
| AcbdA | Peroxisome motility defects | Aspergillus knockout and tagged knock-in |
| ZDHHC | Protein palmitoylation signaling | Point mutation of acyl-CoA binding site |
TANGO2-related metabolic and neurological disease
TANGO2 is an acyl-CoA binding protein, and its dysfunction impairs mitochondrial fatty-acid handling, linking GO:0000062 to a rare inherited disorder with metabolic and neurological features. Research models focus on mitochondrial acyl-CoA flux and stress responses.
Cancer metabolism and gliomagenesis
Acyl-CoA-binding protein fuels gliomagenesis, demonstrating that fatty-acyl-CoA binding can support tumor growth. This makes GO:0000062 a potential target in cancers with lipid metabolic dependencies.
Mitochondrial beta-oxidation disorders
Because fatty-acyl-CoA binding is required for mitochondrial beta-oxidation of saturated fatty acids, defects in this function can contribute to fatty acid oxidation disorders. Short- and medium-chain fatty acid handling is also relevant to energy metabolism disease.
From fatty-acyl-CoA binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of acyl-CoA binding impair beta-oxidation? | Knockout of DBI or TANGO2 in human cells |
| Which residues mediate fatty acyl-CoA binding? | Point mutation of binding pocket residues |
| Can a tagged protein track acyl-CoA binding in live cells? | Knock-in of fluorescent or affinity tag |
| Does overexpression drive oncogenic lipid signaling? | Overexpression of ACBP/DBI in cancer lines |
| How does nutrient state change acyl-CoA binding? | Drosophila ACBP6 knockout and feeding regimes |
| Is acyl-CoA binding required for organelle motility? | Aspergillus AcbdA knockout and imaging |
How to Study the fatty-acyl-CoA binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescence lipid binding assay | Binding affinity for fatty-acyl-CoA | ACBP/DBI and TANGO2 characterization |
| Isothermal titration calorimetry | Thermodynamics of ligand binding | Acyl chain specificity |
| Cryo-EM / crystallography | Three-dimensional binding site | Palmitoyltransferase recognition |
| Acyl-CoA profiling by LC-MS | Cellular acyl-CoA species | Beta-oxidation flux |
| Seahorse respirometry | Mitochondrial oxidation rate | Metabolic phenotyping |
| Live-cell imaging | Organelle motility and protein localization | Peroxisome hitchhiking |
| Drosophila genetics | Nutrient adaptation phenotypes | ACBP6 function in vivo |
| CRISPR knockout screening | Gene requirement for lipid metabolism | Cancer dependency studies |
Lipid binding assays
Direct binding of fatty-acyl-CoA to proteins can be measured using fluorescence-based lipid binding assays and isothermal titration calorimetry, as applied to ACBP/DBI and TANGO2. These methods define affinity and specificity for different acyl chain lengths.
Structural biology
Crystal structures and cryo-EM maps reveal the bivalent recognition of fatty acyl-CoA by palmitoyltransferases and the acyl-CoA binding pocket of carrier proteins. Structural work guides point-mutation design.
Metabolic flux and beta-oxidation
Seahorse respirometry, isotope tracing, and acyl-CoA profiling measure how fatty-acyl-CoA binding affects mitochondrial beta-oxidation. These readouts connect GO:0000062 to energy metabolism.
Imaging and organelle tracking
Live-cell imaging of tagged acyl-CoA binding proteins reveals peroxisome hitchhiking and membrane dynamics. Drosophila imaging links ACBP6 to tissue plasticity.
How CRISPR Can Be Used to Study GO:0000062 fatty-acyl-CoA binding
Knockout
CRISPR knockout of DBI, TANGO2, or ACBP6 can test whether fatty-acyl-CoA binding is required for beta-oxidation, nutrient adaptation, or organelle motility. Knockout models are the first step to establish causality for GO:0000062.
Point Mutation
Point mutations in the acyl-CoA binding pocket can separate binding from downstream catalysis or acylation, as suggested by structural studies of palmitoyltransferases. These models refine the molecular function annotation.
Knock-in
Knock-in of fluorescent or affinity tags allows tracking of acyl-CoA binding proteins in live cells and tissues, as used for AcbdA in Aspergillus and TANGO2 studies. Tagged knock-ins preserve endogenous regulation.
Overexpression
Overexpression of ACBP/DBI can drive oncogenic lipid signaling in glioma models, linking fatty-acyl-CoA binding to cancer. Overexpression in Drosophila can reveal tissue plasticity effects.
How EDITGENE Supports fatty-acyl-CoA binding Research
Researchers studying fatty-acyl-CoA binding-related genes often need to determine whether a candidate gene is causally involved in lipid metabolism, cancer, or organelle biology. EDITGENE provides publication-ready CRISPR models and screening services to test these hypotheses with rigor.
Contact EDITGENE today to design your custom CRISPR model for fatty-acyl-CoA binding research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DBI Knockout HEK293 Cell Line | EDJ-KQ2682 | Human | 1622 | Details Get a Quote |
| ACADVL Knockout HEK293 Cell Line | EDJ-KQ3277 | Human | 37 | Details Get a Quote |
| ECI2 Knockout HEK293 Cell Line | EDJ-KQ3819 | Human | 10455 | Details Get a Quote |
| GCDH Knockout HEK293 Cell Line | EDJ-KQ4688 | Human | 2639 | Details Get a Quote |
| SOAT2 Knockout HEK293 Cell Line | EDJ-KQ5535 | Human | 8435 | Details Get a Quote |
| SCP2 Knockout HEK293 Cell Line | EDJ-KQ5722 | Human | 6342 | Details Get a Quote |
| SOAT1 Knockout HEK293 Cell Line | EDJ-KQ5816 | Human | 6646 | Details Get a Quote |
| ACOT7 Knockout HEK293 Cell Line | EDJ-KQ7375 | Human | 11332 | Details Get a Quote |
| ACBD6 Knockout HEK293 Cell Line | EDJ-KQ9284 | Human | 84320 | Details Get a Quote |
| ACBD5 Knockout HEK293 Cell Line | EDJ-KQ10739 | Human | 91452 | Details Get a Quote |
| ACBD3 Knockout HEK293 Cell Line | EDJ-KQ11482 | Human | 64746 | Details Get a Quote |
| ACBD4 Knockout HEK293 Cell Line | EDJ-KQ12255 | Human | 79777 | Details Get a Quote |
| ACBD7 Knockout HEK293 Cell Line | EDJ-KQ12256 | Human | 414149 | Details Get a Quote |
| ECI2 Knockout A-549 Cell Line | EDJ-KQ25952 | Human | 10455 | Details Get a Quote |
| ECI2 Knockout HCT 116 Cell Line | EDJ-KQ25953 | Human | 10455 | Details Get a Quote |
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Frequently Asked Questions About fatty-acyl-CoA binding
What is fatty-acyl-CoA binding?
Fatty-acyl-CoA binding (GO:0000062) is the molecular function of reversibly binding a fatty-acyl-CoA, a coenzyme A thioester of a fatty acid.
What genes are involved in fatty-acyl-CoA binding?
Key genes include DBI (ACBP), TANGO2, ACBP6, and AcbdA, as well as palmitoyltransferases that recognize fatty acyl-CoA.
What is the GO ID for fatty-acyl-CoA binding?
The GO ID is GO:0000062, a molecular_function term.
How is fatty-acyl-CoA binding related to beta-oxidation?
Fatty-acyl-CoA binding delivers acyl-CoA to mitochondrial beta-oxidation of saturated fatty acids.
Is fatty-acyl-CoA binding involved in cancer?
Yes, acyl-CoA-binding protein fuels gliomagenesis, linking this function to cancer metabolism.
What diseases are linked to fatty-acyl-CoA binding?
TANGO2-related metabolic and neurological disease and mitochondrial beta-oxidation disorders are linked to this function.
How can I study fatty-acyl-CoA binding in the lab?
Use lipid binding assays, structural biology, metabolic flux measurements, imaging, and CRISPR models.
What model organisms are used for fatty-acyl-CoA binding?
Drosophila ACBP6 and Aspergillus AcbdA are established models for nutrient adaptation and peroxisome biology.
What is the difference between fatty-acyl-CoA binding and fatty acid binding?
Fatty-acyl-CoA binding involves the CoA thioester, whereas fatty acid binding involves the free fatty acid; ACBP and FABP are distinct protein families.
Can CRISPR knockout help study fatty-acyl-CoA binding?
Yes, knockout of DBI, TANGO2, or ACBP6 tests the requirement for this function in metabolism and disease models.
Conclusion
GO:0000062 fatty-acyl-CoA binding is a central molecular function that governs how cells handle acyl-CoA for energy metabolism, membrane trafficking, and signaling. Verified studies show that acyl-CoA binding proteins such as ACBP/DBI, TANGO2, ACBP6, and AcbdA are required for diverse processes from beta-oxidation to peroxisome motility. The function is also implicated in cancer and inherited metabolic disease, making it a high-value target for CRISPR-based research. By combining knockout, point-mutation, knock-in, overexpression, and screening approaches, researchers can dissect the precise roles of fatty-acyl-CoA binding in health and disease.
References
- 1. Lujan AL et al.. 2025. TANGO2 is an acyl-CoA binding protein.. J Cell Biol 224(5) PMID: 40015245
- 2. Bi J et al.. 2019. Acyl-CoA-Binding Protein Fuels Gliomagenesis.. Cell Metab 30(2):229-230 PMID: 31390546
- 3. Adeva-Andany MM et al.. 2019. Mitochondrial β-oxidation of saturated fatty acids in humans.. Mitochondrion 46:73-90 PMID: 29551309
- 4. Lee CJ et al.. 2022. Bivalent recognition of fatty acyl-CoA by a human integral membrane palmitoyltransferase.. Proc Natl Acad Sci U S A 119(7) PMID: 35140179
- 5. Knudsen J. 1990. Acyl-CoA-binding protein (ACBP) and its relation to fatty acid-binding protein (FABP): an overview.. Mol Cell Biochem 98(1-2):217-23 PMID: 2266962
- 6. Schönfeld P et al.. 2016. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective.. J Lipid Res 57(6):943-54 PMID: 27080715
- 7. Li X et al.. 2023. A distinct Acyl-CoA binding protein (ACBP6) shapes tissue plasticity during nutrient adaptation in Drosophila.. Nat Commun 14(1):7599 PMID: 37989752
- 8. Driscoll BE et al.. 2025. Acyl-CoA-binding protein AcbdA is required for peroxisome hitchhiking on early endosomes in Aspergillus nidulans.. Mol Biol Cell 36(12):br26 PMID: 40901736
