GO:0015880 coenzyme A transport: Subcellular Flux, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015880 (coenzyme A transport) describes the directed movement of coenzyme A (CoA) into, out of, or within a cell by transporters or pores.
• CoA is an essential acyl carrier in acylation and acyl-transfer reactions, and its transport between compartments is required for lipid trafficking and metabolic remodeling.
• Mitochondrial and peroxisomal CoA transport is mediated by specific carrier proteins, including SLC25A1 and peroxisomal cofactor transporters.
• CoA availability influences ferroptosis susceptibility through CoAlation of mitochondrial thioredoxin reductase and modulation of xCT antiporter function.
• ACSS2 can translocate to the nucleus and promote gene transcription for lysosomal biogenesis and autophagy, linking CoA metabolism to epigenetic regulation.
• Malonyl-CoA affects insulin-stimulated glucose transport in myotubes, connecting CoA transport and metabolism to insulin sensitivity.
Description
Coenzyme A (CoA) is a ubiquitous cofactor that serves as an acyl carrier in numerous acylation and acyl-transfer reactions, often forming thiol esters as intermediates. The directed movement of CoA across cellular membranes and between subcellular compartments is defined by the Gene Ontology term GO:0015880, coenzyme A transport. This process is essential for maintaining compartment-specific pools of CoA and its derivatives, which are required for fatty acid synthesis, oxidation, and protein modification. Researchers study coenzyme A transport because it directly impacts metabolic homeostasis, lipid trafficking, and cell survival. For example, preservation of acyl-CoA pools attenuates pathological and metabolic cardiac remodeling through selective lipid trafficking. In addition, CoA protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase, highlighting a role in redox regulation and cell death. The transport of CoA and its precursors between the cytosol, mitochondria, and peroxisomes is therefore a critical node in metabolic and signaling networks. Understanding the molecular machinery and regulation of coenzyme A transport can reveal therapeutic targets for metabolic disorders, cancer, and neurodegeneration. This article integrates authoritative GO annotations with published literature to provide a research-grade overview of GO:0015880, its associated genes, and experimental approaches for its study.
coenzyme A transport At A Glance
| GO ID | GO:0015880 |
|---|---|
| GO term | coenzyme A transport |
| Ontology | biological_process |
| Synonym | none |
| Major function | Directed movement of coenzyme A across membranes or between cellular compartments via transporters or pores |
| Definition source | QuickGO |
| Related cellular components | Mitochondrial inner membrane, peroxisomal membrane, cytosol |
| Related molecular functions | CoA transmembrane transporter activity, acyl carrier activity |
| Associated diseases | Cardiac remodeling, ferroptosis-related pathologies, metabolic disorders |
What Is GO:0015880?
GO:0015880, coenzyme A transport, is defined as the directed movement of coenzyme A into, out of, or within a cell, or between cells, by means of some agent such as a transporter or pore. Coenzyme A, chemically 3'-phosphoadenosine-(5')diphospho(4')pantatheine, is an acyl carrier in many acylation and acyl-transfer reactions in which the intermediate is a thiol ester.
Why Is coenzyme A transport Important in Cell Biology?
Coenzyme A transport is fundamental for compartmentalized metabolism because CoA and its thioester derivatives cannot freely diffuse across lipid bilayers. The directed movement of CoA ensures that mitochondrial, peroxisomal, and cytosolic pools are supplied for fatty acid oxidation, lipid synthesis, and protein acylation. Disruption of CoA transport or availability has been linked to pathological cardiac remodeling, ferroptosis, and altered insulin-stimulated glucose transport, underscoring its broad physiological significance.
• Maintains compartment-specific CoA pools required for fatty acid synthesis and oxidation.
• Supports selective lipid trafficking and protects against pathological cardiac remodeling.
• Regulates ferroptosis susceptibility through CoAlation of mitochondrial thioredoxin reductase.
• Influences cytosolic acetyl-CoA levels and FSP1 acetylation, affecting ferroptosis.
• Links CoA metabolism to nuclear gene transcription for lysosomal biogenesis and autophagy.
• Peroxisomal cofactor transport is essential for peroxisomal metabolic functions.
• Modulates airway basal progenitor cell function via glycolytic-epigenetic reprogramming.
• Malonyl-CoA affects insulin-stimulated glucose transport in myotubes.
• NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation.
• Provides targets for therapeutic intervention in metabolic and cardiovascular diseases.
What Happens During coenzyme A transport?
Synthesis and Intracellular Distribution of CoA
In simple terms: CoA is made inside cells and then moved to where it is needed.
Coenzyme A is synthesized in the cytosol and must be distributed to various organelles, including mitochondria and peroxisomes, to participate in compartment-specific metabolic reactions. The transport of CoA across organellar membranes is mediated by specific carrier proteins that facilitate its directed movement. This distribution is critical for maintaining the distinct pools of CoA required for fatty acid oxidation in mitochondria and lipid synthesis in the cytosol.
Mitochondrial CoA Transport
In simple terms: Special proteins carry CoA into mitochondria.
Mitochondrial CoA transport involves carrier proteins such as SLC25A1, which maintains cytosolic acetyl-CoA levels and regulates ferroptosis susceptibility via FSP1 acetylation. The transport of CoA into mitochondria is essential for the formation of acyl-CoA intermediates used in the tricarboxylic acid cycle and fatty acid oxidation. Preservation of acyl-CoA pools through selective lipid trafficking attenuates pathological and metabolic cardiac remodeling.
Peroxisomal CoA Transport
In simple terms: CoA also needs to get into peroxisomes for specific reactions.
Peroxisomal cofactor transport is required for peroxisomal metabolic pathways, including fatty acid oxidation and plasmalogen synthesis. Specific transporters mediate the movement of CoA and its precursors across the peroxisomal membrane. Defects in peroxisomal cofactor transport can lead to metabolic disorders, highlighting the importance of GO:0015880 in peroxisomal function.
CoA in Ferroptosis Regulation
In simple terms: CoA transport affects how cells die from iron-dependent lipid damage.
Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase, a process that depends on adequate CoA availability and transport. Additionally, NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation, linking CoA transport to redox homeostasis. SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation, further connecting CoA transport to cell death pathways.
Nuclear and Epigenetic Roles of CoA
In simple terms: CoA can move to the nucleus and influence gene activity.
Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy, demonstrating that CoA metabolism can directly impact nuclear processes. This nuclear role of CoA links its transport and availability to epigenetic regulation and autophagic flux. Mitochondrial pyruvate carriers control airway basal progenitor cell function through glycolytic-epigenetic reprogramming, indicating that CoA-related metabolic flux influences stem cell fate.
Key Genes Involved in GO:0015880 coenzyme A transport
The following genes and proteins are involved in coenzyme A transport and related metabolic pathways, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC25A1 | Mitochondrial carrier for acetyl-CoA/CoA | Maintains cytosolic acetyl-CoA and regulates ferroptosis via FSP1 acetylation |
| ACLY | ATP-citrate lyase generates acetyl-CoA | Supports cytosolic acetyl-CoA pools and ferroptosis susceptibility |
| ACSS2 | Acetyl-CoA synthetase 2 | Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy |
| NINJ1 | Regulates ferroptosis via xCT antiporter interaction | Modulates CoA levels and ferroptosis |
| SLC25A family members | Mitochondrial carrier proteins | Transport CoA and related cofactors across mitochondrial membranes |
| Peroxisomal transporters | Cofactor transport into peroxisomes | Essential for peroxisomal metabolism |
| MPC1/MPC2 | Mitochondrial pyruvate carriers | Control airway basal progenitor cell function via glycolytic-epigenetic reprogramming |
| Thioredoxin reductase (TXNRD2) | Mitochondrial redox regulation | CoAlation of TXNRD2 protects against ferroptosis |
| FSP1 | Ferroptosis suppressor protein 1 | Acetylation regulated by SLC25A1/ACLY affects ferroptosis |
| xCT (SLC7A11) | Cystine/glutamate antiporter | Interacts with NINJ1 and modulates CoA |
| ACACA/ACACB | Acetyl-CoA carboxylase | Produces malonyl-CoA affecting insulin-stimulated glucose transport |
| CPT1A | Carnitine palmitoyltransferase 1A | Uses acyl-CoA for mitochondrial fatty acid oxidation |
| ACADM | Medium-chain acyl-CoA dehydrogenase | Beta-oxidation of acyl-CoA in mitochondria |
| HADHA | Trifunctional enzyme subunit alpha | Mitochondrial fatty acid oxidation |
| PDHA1 | Pyruvate dehydrogenase E1 alpha | Generates acetyl-CoA from pyruvate |
| SLC25A20 | Carnitine-acylcarnitine translocase | Transport of acyl-carnitine for fatty acid oxidation |
| IDH2 | Isocitrate dehydrogenase 2 | Mitochondrial NADPH production linked to CoA metabolism |
How Is coenzyme A transport Regulated?
Coenzyme A transport is regulated at multiple levels, including the expression and activity of transporter proteins such as SLC25A1 and peroxisomal cofactor transporters. The availability of CoA precursors and the activity of biosynthetic enzymes also influence transport dynamics. Additionally, signaling pathways such as those involving ACSS2 and its nuclear translocation can modulate CoA-related gene transcription in response to metabolic cues. Ferroptosis-related signals, including xCT antiporter activity and NINJ1, can impact CoA modulation and transport.
coenzyme A transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC25A1 | Ferroptosis susceptibility, metabolic disorders | Knockout or point-mutation cell lines |
| ACSS2 | Autophagy, lysosomal biogenesis, neurodegeneration | Overexpression and knockout models |
| NINJ1 | Ferroptosis, cancer | Knockout and knock-in models |
| ACACA/ACACB | Insulin resistance, metabolic syndrome | Point-mutation and overexpression models |
| TXNRD2 | Ferroptosis, oxidative stress | CoAlation site knock-in models |
Cardiac Remodeling and Metabolic Heart Disease
Preservation of acyl coenzyme A attenuates pathological and metabolic cardiac remodeling through selective lipid trafficking, indicating that CoA transport and availability are critical in heart disease. Disrupted CoA homeostasis can lead to impaired fatty acid oxidation and lipid accumulation, contributing to cardiac dysfunction.
Ferroptosis and Cancer
Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase, and SLC25A1/ACLY maintain cytosolic acetyl-CoA to regulate ferroptosis susceptibility via FSP1 acetylation. NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation, linking CoA transport to cancer cell death pathways.
Metabolic Disorders and Insulin Resistance
Malonyl coenzyme A affects insulin-stimulated glucose transport in myotubes, suggesting that CoA derivatives influence glucose metabolism and insulin sensitivity. Dysregulation of CoA transport may therefore contribute to metabolic disorders such as type 2 diabetes.
Neurodegeneration and Autophagy
Nucleus-translocated ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy, processes that are impaired in neurodegenerative diseases. Proper CoA transport and metabolism are essential for neuronal survival and proteostasis.
From coenzyme A transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC25A1 affect CoA transport and ferroptosis? | SLC25A1 knockout cell line |
| How does ACSS2 nuclear translocation impact autophagy? | ACSS2 overexpression and knockout models |
| What is the role of NINJ1 in CoA modulation during ferroptosis? | NINJ1 knockout and point-mutation models |
| Does malonyl-CoA alter insulin-stimulated glucose transport? | ACACA/ACACB overexpression in myotubes |
| How does CoAlation of TXNRD2 protect against ferroptosis? | TXNRD2 point-mutation knock-in |
| What is the impact of peroxisomal CoA transport defects? | Peroxisomal transporter knockout models |
How to Study the coenzyme A transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Stable isotope tracing | Metabolic flux of CoA and acyl-CoA | Quantifying CoA transport in cells |
| CoAlation proteomics | Proteins modified by CoA | Identifying CoA-dependent redox regulation |
| Live-cell imaging | Subcellular localization of transporters | Tracking CoA transport dynamics |
| CRISPR knockout screening | Genes required for CoA transport | Discovering novel regulators |
| RNA-seq | Transcriptional changes upon CoA perturbation | Analyzing gene expression in response to CoA levels |
| Ribo-seq | Translation efficiency of CoA-related genes | Studying translational control |
| Metabolomics | Levels of CoA and intermediates | Assessing metabolic impact of transport defects |
| Bioinformatics pathway analysis | Enrichment of GO:0015880 | Interpreting omics data |
Metabolic Flux Analysis
Metabolic flux analysis using stable isotope tracing can quantify CoA transport and utilization across compartments. This method helps researchers understand how CoA pools are maintained and redistributed under different conditions.
Proteomics and CoAlation Profiling
Proteomic approaches can identify proteins that undergo CoAlation, such as mitochondrial thioredoxin reductase, providing insights into CoA-dependent regulation. CoAlation profiling is particularly useful for studying ferroptosis and redox signaling.
Imaging of CoA Transporters
Fluorescence microscopy and live-cell imaging of tagged CoA transporters can reveal their subcellular localization and dynamics. This is essential for understanding how CoA is directed to specific organelles.
Genetic Screens and CRISPR Libraries
CRISPR library screening can identify genes required for CoA transport and metabolism, such as SLC25A1 and ACLY. Bioinformatics analysis of screening data can uncover pathways linked to GO:0015880.
How CRISPR Can Be Used to Study GO:0015880 coenzyme A transport
Knockout
CRISPR knockout of genes such as SLC25A1 or NINJ1 can disrupt coenzyme A transport and reveal its role in ferroptosis and metabolic remodeling. Knockout models are valuable for studying loss-of-function phenotypes in relevant cell types.
Point Mutation
Point mutations can be introduced into CoA transporter genes to mimic disease-associated variants or to abrogate specific post-translational modification sites, such as CoAlation sites in TXNRD2. These models help dissect the precise molecular mechanisms of CoA transport.
Knock-in
Knock-in of tagged CoA transporters (e.g., GFP-SLC25A1) allows visualization and affinity purification of transport complexes. This approach is useful for studying the dynamic localization and interactions of CoA transport machinery.
Overexpression
Overexpression of ACSS2 or ACLY can increase CoA availability and alter autophagy and ferroptosis susceptibility. Overexpression models are used to test gain-of-function effects on CoA transport and downstream pathways.
How EDITGENE Supports coenzyme A transport Research
Researchers studying coenzyme A transport-related genes often need to determine whether a candidate gene is causally involved in metabolic regulation, ferroptosis, or cardiac remodeling. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for coenzyme A transport research.
Frequently Asked Questions About coenzyme A transport
What is coenzyme A transport?
Coenzyme A transport (GO:0015880) is the directed movement of coenzyme A into, out of, or within a cell, or between cells, by means of transporters or pores.
What genes are involved in coenzyme A transport?
Genes such as SLC25A1, ACLY, ACSS2, NINJ1, and peroxisomal transporters are involved in coenzyme A transport and related metabolism.
How does coenzyme A transport affect ferroptosis?
Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase, and SLC25A1/ACLY regulate ferroptosis susceptibility via FSP1 acetylation.
What is the role of SLC25A1 in coenzyme A transport?
SLC25A1 is a mitochondrial carrier that maintains cytosolic acetyl-CoA and regulates ferroptosis susceptibility.
Can coenzyme A transport be studied with CRISPR?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models can be used to study genes involved in coenzyme A transport.
What diseases are linked to coenzyme A transport?
Cardiac remodeling, ferroptosis-related cancers, metabolic disorders, and neurodegeneration have been linked to coenzyme A transport.
How is coenzyme A transport regulated?
It is regulated by the expression of transporters like SLC25A1, precursor availability, and signaling pathways involving ACSS2 and NINJ1.
What methods are used to study coenzyme A transport?
Metabolic flux analysis, proteomics, imaging, and CRISPR screening are commonly used.
What is the GO ID for coenzyme A transport?
The GO ID is GO:0015880.
Why is coenzyme A transport important for metabolism?
It ensures compartment-specific CoA pools for fatty acid synthesis, oxidation, and protein acylation.
Conclusion
Coenzyme A transport (GO:0015880) is a critical biological process that maintains compartmentalized CoA pools for diverse metabolic and signaling functions. Research has linked it to cardiac remodeling, ferroptosis, autophagy, and insulin sensitivity, highlighting its broad physiological relevance. Understanding the genes and mechanisms involved, such as SLC25A1, ACSS2, and NINJ1, provides opportunities for therapeutic intervention. EDITGENE offers a comprehensive suite of CRISPR services, including knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics, to support mechanistic studies of coenzyme A transport and its associated genes.
References
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- 2. Lin CC et al.. 2025. Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.. J Clin Invest 135(19) PMID: 40694424
- 3. Li W et al.. 2025. SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.. EMBO J 44(6):1641-1662 PMID: 39881208
- 4. Li X et al.. 2017. Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy.. Mol Cell 66(5):684-697.e9 PMID: 28552616
- 5. Plett A et al.. 2020. Peroxisomal Cofactor Transport.. Biomolecules 10(8) PMID: 32806597
- 6. Li Y et al.. 2025. Mitochondrial pyruvate carriers control airway basal progenitor cell function through glycolytic-epigenetic reprogramming.. Cell Stem Cell 32(1):105-120.e6 PMID: 39426380
- 7. Patil PB et al.. 2007. Malonyl coenzyme A affects insulin-stimulated glucose transport in myotubes.. Arch Physiol Biochem 113(1):13-24 PMID: 17522981
- 8. Chen SY et al.. 2024. NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation.. Cell Death Dis 15(10):755 PMID: 39424803
