GO:0015909 long-chain fatty acid transport: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015909 describes the directed movement of long-chain fatty acids (13 to 22 carbons) into, out of, or within a cell, or between cells, via transporters or pores.
• Membrane-associated proteins such as CD36, FATP/SLC27A family members, and FABPs are central to cellular long-chain fatty acid uptake and trafficking.
• Long-chain fatty acid transport is essential for energy production, membrane synthesis, and lipid signaling, and its dysregulation is linked to cancer, metabolic disorders, and infections.
• SLC27A1-mediated long-chain fatty acid transport can enhance DAG-3-P synthesis and accelerate colorectal cancer metastasis, highlighting its role in tumor progression.
• In Mycobacterium tuberculosis, long-chain multiple methyl-branched fatty acid-containing lipids are involved in biosynthesis, transport, and host-pathogen interactions.
• CRISPR-based knockout, knock-in, point mutation, and overexpression models enable causal interrogation of genes involved in long-chain fatty acid transport.
Description
Long-chain fatty acid transport (GO:0015909) is the biological process that mediates the directed movement of long-chain fatty acids (LCFAs), defined as fatty acids with aliphatic tails of 13 to 22 carbons, into, out of, or within cells, or between cells, through transporters or pores. This process is fundamental for cellular energy homeostasis, membrane lipid synthesis, and the generation of lipid signaling molecules. Because LCFAs are hydrophobic and cannot freely diffuse across membranes at sufficient rates, dedicated transport proteins are required to facilitate their uptake and distribution. Research over the past decades has identified multiple families of membrane-associated fatty acid transport proteins, including the CD36 scavenger receptor, the fatty acid transport protein (FATP/SLC27A) family, and plasma membrane fatty acid-binding proteins. These proteins are not merely passive conduits; they are integrated into signaling networks that regulate immune cell metabolism, cancer progression, and metabolic disease. Understanding GO:0015909 is therefore critical for researchers studying lipid metabolism, energy balance, and diseases ranging from colorectal cancer to mycobacterial infections. The process also intersects with carnitine transport and mitochondrial fatty acid oxidation, as LCFAs must be activated and shuttled into mitochondria for beta-oxidation. This article provides a research-grade overview of the mechanisms, key genes, regulatory features, disease associations, and experimental methods used to study long-chain fatty acid transport.
long-chain fatty acid transport At A Glance
| GO ID | GO:0015909 |
|---|---|
| GO term | long-chain fatty acid transport |
| Ontology | biological_process |
| Synonym | none |
| Major function | Directed movement of long-chain fatty acids (13-22 carbons) across membranes via transporters or pores |
| Definition source | QuickGO |
| Related processes | Fatty acid oxidation, lipid metabolism, carnitine transport, membrane lipid synthesis |
| Key protein families | CD36, FATP/SLC27A, FABP, membrane-associated fatty acid-binding proteins |
| Cellular context | Plasma membrane, cytoplasm, mitochondria, peroxisomes |
What Is GO:0015909?
GO:0015909, long-chain fatty acid transport, is defined as the directed movement of a long-chain fatty acid into, out of, or within a cell, or between cells, by means of some agent such as a transporter or pore. A long-chain fatty acid has an aliphatic tail containing 13 to 22 carbons. This process encompasses the translocation of LCFAs across biological membranes and their distribution within cellular compartments, facilitated by membrane-associated transport proteins.
Why Is long-chain fatty acid transport Important in Cell Biology?
Long-chain fatty acid transport is a cornerstone of cellular and systemic lipid homeostasis, directly influencing energy production, membrane biogenesis, and signaling. Dysregulation of this process contributes to a wide range of pathologies, including cancer, metabolic syndrome, and infectious diseases. Because LCFAs are essential substrates for beta-oxidation and precursors for complex lipids, their transport must be tightly controlled to match cellular demands. Moreover, transport proteins such as CD36 and SLC27A1 have emerged as signaling receptors that modulate immune cell fate and tumor metastasis, making GO:0015909 a high-priority area for therapeutic targeting.
• Provides essential fatty acids for mitochondrial beta-oxidation and ATP production.
• Supplies precursors for membrane phospholipid and sphingolipid synthesis.
• Regulates immune cell metabolism and fate through CD36 signaling.
• Promotes cancer metastasis via SLC27A1-mediated DAG-3-P synthesis in colorectal cancer.
• Contributes to Mycobacterium tuberculosis lipid biosynthesis and host-pathogen interactions.
• Involved in metabolic disorders such as obesity, insulin resistance, and cardiovascular disease.
• Affects drug delivery and bioavailability of lipophilic compounds.
• Serves as a target for engineering microbial production of dicarboxylic acids.
• Modulates inflammatory responses through fatty acid transport proteins.
• Offers opportunities for CRISPR-based functional genomics and therapeutic intervention.
What Happens During long-chain fatty acid transport?
Recognition and Binding at the Plasma Membrane
In simple terms: Long-chain fatty acids first attach to proteins on the cell surface.
The initial step of long-chain fatty acid transport involves the recognition and binding of LCFAs to membrane-associated proteins such as CD36, FATPs (SLC27A family), and plasma membrane fatty acid-binding protein (FABPpm). CD36 acts as a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate. These proteins facilitate the uptake of LCFAs, which are otherwise poorly soluble in aqueous environments.
Translocation Across the Plasma Membrane
In simple terms: The fatty acid is moved across the outer membrane of the cell.
Following binding, LCFAs are translocated across the plasma membrane by transporter proteins or pores. This step may involve facilitated diffusion or active transport mechanisms, depending on the cell type and metabolic state. The FATP family members, including SLC27A1, are implicated in this translocation process and can also activate LCFAs by converting them to acyl-CoA.
Intracellular Trafficking and Activation
In simple terms: Inside the cell, the fatty acid is carried to where it is needed and chemically activated.
Once inside the cell, LCFAs are bound by cytoplasmic fatty acid-binding proteins (FABPs) and trafficked to various organelles, including mitochondria, peroxisomes, and the endoplasmic reticulum. Activation to acyl-CoA by acyl-CoA synthetases (e.g., SLC27A1) is required for further metabolism, including beta-oxidation and lipid synthesis. In colorectal cancer, SLC27A1-mediated transport enhances DAG-3-P synthesis, accelerating metastasis.
Mitochondrial Import and Beta-Oxidation
In simple terms: Fatty acids are shuttled into mitochondria to be burned for energy.
Long-chain acyl-CoAs are transported into mitochondria via the carnitine shuttle system, involving carnitine palmitoyltransferase 1 (CPT1), carnitine-acylcarnitine translocase, and CPT2. Carnitine transport is essential for this process, and defects lead to impaired fatty acid oxidation. Inside mitochondria, beta-oxidation generates acetyl-CoA, which enters the TCA cycle for ATP production.
Transport in Microbial and Specialized Systems
In simple terms: Microbes and specialized cells also use similar transport strategies.
In Candida tropicalis, engineering fatty transporters increases long-chain dicarboxylic acid production, demonstrating the biotechnological relevance of LCFA transport. In Mycobacterium tuberculosis, long-chain multiple methyl-branched fatty acid-containing lipids are synthesized, transported, and regulated, contributing to the unique cell envelope and pathogenesis.
Key Genes Involved in GO:0015909 long-chain fatty acid transport
The following genes and proteins are central to long-chain fatty acid transport and are frequently studied in metabolic, cancer, and infectious disease research.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CD36 | Fatty acid translocase; binds and transports LCFAs; signaling receptor | Immune cell metabolism, cancer, cardiovascular disease |
| SLC27A1 (FATP1) | Fatty acid transport protein; enhances LCFA uptake and activation | Colorectal cancer metastasis, DAG-3-P synthesis |
| SLC27A2 (FATP2) | Very long-chain acyl-CoA synthetase; LCFA transport and activation | Metabolic disorders, cancer |
| SLC27A3 (FATP3) | Fatty acid transport protein | Lipid metabolism |
| SLC27A4 (FATP4) | Fatty acid transport protein; intestinal lipid absorption | Metabolic syndrome, skin disorders |
| SLC27A5 (FATP5) | Liver-specific fatty acid transport protein | Hepatic lipid metabolism |
| SLC27A6 (FATP6) | Heart-specific fatty acid transport protein | Cardiac lipid uptake |
| FABP1 (L-FABP) | Liver fatty acid-binding protein; intracellular trafficking | Hepatic steatosis, cancer |
| FABP2 (I-FABP) | Intestinal fatty acid-binding protein | Intestinal lipid absorption |
| FABP3 (H-FABP) | Heart fatty acid-binding protein | Cardiac metabolism |
| FABP4 (A-FABP) | Adipocyte fatty acid-binding protein | Obesity, insulin resistance |
| FABP5 | Epidermal fatty acid-binding protein | Psoriasis, cancer |
| CPT1A | Carnitine palmitoyltransferase 1A; mitochondrial import of LCFAs | Fatty acid oxidation disorders |
| CPT2 | Carnitine palmitoyltransferase 2; inner mitochondrial membrane transport | CPT2 deficiency, rhabdomyolysis |
| SLC25A20 (CACT) | Carnitine-acylcarnitine translocase | Fatty acid oxidation defects |
| ACSL1 | Long-chain acyl-CoA synthetase 1 | Lipid synthesis, beta-oxidation |
| ACSL4 | Long-chain acyl-CoA synthetase 4 | Ferroptosis, cancer |
How Is long-chain fatty acid transport Regulated?
Long-chain fatty acid transport is regulated at multiple levels, including transcriptional control by nuclear receptors such as PPARs and SREBP-1c, post-translational modifications, and hormonal signals (e.g., insulin, leptin). CD36 expression and localization are modulated by inflammatory cytokines and metabolic stress, influencing immune cell function. In cancer, SLC27A1 expression can be upregulated to support increased lipid demand for membrane synthesis and signaling. The carnitine shuttle, which is essential for mitochondrial LCFA import, is regulated by malonyl-CoA inhibition of CPT1, linking fatty acid transport to overall energy status. Additionally, microbial fatty acid transport systems are regulated in response to environmental conditions and host factors.
long-chain fatty acid transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC27A1 | Colorectal cancer metastasis | Knockout and overexpression in HCT116 or SW480 cells |
| CD36 | Immune cell metabolism, atherosclerosis | Conditional knockout in macrophages |
| CPT1A | Fatty acid oxidation disorders | Point mutation knock-in in patient-derived fibroblasts |
| SLC25A20 | Carnitine-acylcarnitine translocase deficiency | Knockout in HepG2 cells |
| FABP4 | Obesity and insulin resistance | Overexpression in adipocytes |
Cancer
Long-chain fatty acid transport supports the high metabolic demands of cancer cells. SLC27A1-mediated LCFA transport enhances DAG-3-P synthesis and accelerates colorectal cancer metastasis. CD36 has been implicated in immune cell metabolism and tumor progression, and FATPs are emerging as therapeutic targets in multiple cancers. Targeting LCFA transport proteins may reduce tumor growth and metastasis.
Metabolic Disorders
Dysregulated LCFA transport contributes to obesity, insulin resistance, and cardiovascular disease. CD36 and FATP family members influence lipid accumulation in adipose tissue, liver, and muscle. Defects in carnitine transport and mitochondrial LCFA import lead to fatty acid oxidation disorders, characterized by hypoketotic hypoglycemia and cardiomyopathy.
Infectious Diseases
Mycobacterium tuberculosis utilizes long-chain multiple methyl-branched fatty acid-containing lipids for cell envelope biosynthesis and pathogenesis, with transport systems playing a critical role in virulence. Understanding these transport mechanisms may reveal new drug targets.
Inflammatory and Immune Disorders
CD36 functions as a signaling receptor that regulates immune cell metabolism and fate, linking LCFA transport to inflammation and immune responses. Altered fatty acid transport in immune cells can affect autoimmunity and host defense.
From long-chain fatty acid transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC27A1 reduce LCFA uptake and metastasis? | CRISPR knockout in colorectal cancer cell lines |
| Does a specific point mutation in CPT1A impair fatty acid oxidation? | Point mutation knock-in in HEK293 or patient cells |
| Can CD36 overexpression enhance immune cell fatty acid uptake? | Knock-in overexpression in Jurkat or primary T cells |
| How does tagged FATP4 localize in live cells? | Tagged knock-in (e.g., GFP) in intestinal epithelial cells |
| Does FABP5 overexpression promote tumor growth? | Overexpression in cancer cell lines |
| Can engineering fatty transporters increase dicarboxylic acid production? | Overexpression in Candida tropicalis |
How to Study the long-chain fatty acid transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss-of-function effects on LCFA transport | Identify essential transporters |
| CRISPR knock-in | Tagged protein localization and function | Study FATP4 trafficking |
| BODIPY-FA uptake assay | Cellular LCFA uptake rate | Screen for transport inhibitors |
| RNA-seq | Transcriptional changes in transport genes | Cancer vs normal tissues |
| Proteomics | Protein abundance and modifications | Identify novel transport regulators |
| 13C-palmitate tracing | Fatty acid oxidation flux | Mitochondrial function |
| Bioinformatics | Gene network and pathway analysis | Identify co-regulated transport genes |
CRISPR-Based Functional Genomics
CRISPR knockout, knock-in, and point mutation models enable precise interrogation of genes involved in long-chain fatty acid transport. For example, knockout of SLC27A1 in colorectal cancer cells can test its role in metastasis. Overexpression of CD36 can assess its impact on immune cell metabolism.
Lipid Uptake Assays
Fluorescent or radiolabeled fatty acid analogs (e.g., BODIPY-FA) are used to measure LCFA uptake in live cells. These assays can be combined with CRISPR perturbations to identify transporters.
Transcriptomics and Proteomics
RNA-seq and proteomics can reveal expression changes in fatty acid transport genes under different conditions, such as cancer progression or metabolic stress. Bioinformatics analysis of public datasets can identify co-regulated gene networks.
Metabolic Flux Analysis
Isotope tracing (e.g., 13C-palmitate) coupled with mass spectrometry measures fatty acid oxidation and incorporation into lipids, providing functional readouts of transport activity.
How CRISPR Can Be Used to Study GO:0015909 long-chain fatty acid transport
Knockout
CRISPR knockout of genes such as SLC27A1 or CD36 can abolish LCFA transport, revealing their contribution to cellular lipid uptake and downstream phenotypes like metastasis. Knockout models are essential for validating causal roles.
Point Mutation
Point mutations in transport proteins (e.g., CPT1A) can mimic human disease variants, allowing functional studies of impaired fatty acid oxidation. CRISPR prime editing or HDR can introduce precise mutations.
Knock-in
Knock-in of tagged versions (e.g., GFP-FATP4) enables live-cell imaging of transporter localization and dynamics. Knock-in of disease-associated alleles can model metabolic disorders.
Overexpression
Overexpression of CD36 or SLC27A1 can enhance LCFA uptake and drive phenotypes such as increased DAG-3-P synthesis and cancer metastasis. Overexpression in microbial systems can improve dicarboxylic acid production.
How EDITGENE Supports long-chain fatty acid transport Research
Researchers studying long-chain fatty acid transport-related genes often need to determine whether a candidate gene is causally involved in LCFA uptake, metabolism, or disease progression. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this discovery process, from gene knockout to precise point mutations and overexpression models.
Contact EDITGENE today to design your custom CRISPR model for long-chain fatty acid transport research.
Frequently Asked Questions About long-chain fatty acid transport
What is long-chain fatty acid transport?
Long-chain fatty acid transport (GO:0015909) is the directed movement of fatty acids with 13 to 22 carbons into, out of, or within cells, or between cells, via transporters or pores.
What genes are involved in long-chain fatty acid transport?
Key genes include CD36, SLC27A1 (FATP1), other FATP family members, FABPs, CPT1A, and SLC25A20.
How is long-chain fatty acid transport regulated?
It is regulated by nuclear receptors (PPARs, SREBP), hormones, and metabolic signals such as malonyl-CoA inhibition of CPT1.
What diseases are associated with defective long-chain fatty acid transport?
Diseases include cancer, metabolic disorders, fatty acid oxidation defects, and infectious diseases like tuberculosis.
What methods are used to study long-chain fatty acid transport?
Methods include CRISPR knockout/knock-in, fluorescent fatty acid uptake assays, RNA-seq, proteomics, and metabolic flux analysis.
Can CRISPR be used to study long-chain fatty acid transport?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect gene function in LCFA transport.
What is the role of CD36 in long-chain fatty acid transport?
CD36 is a fatty acid translocase that binds and transports LCFAs and also functions as a signaling receptor regulating immune cell metabolism.
How does SLC27A1 contribute to cancer?
SLC27A1-mediated LCFA transport enhances DAG-3-P synthesis and accelerates colorectal cancer metastasis.
What is the connection between long-chain fatty acid transport and mitochondria?
LCFAs must be transported into mitochondria via the carnitine shuttle for beta-oxidation, a process involving CPT1A, CACT, and CPT2.
How can I create a knockout model for a long-chain fatty acid transport gene?
EDITGENE provides custom CRISPR knockout services for genes like SLC27A1, CD36, and FABPs, with validated cell lines and functional assays.
Conclusion
Long-chain fatty acid transport (GO:0015909) is a fundamental biological process that governs cellular lipid uptake and metabolism, with far-reaching implications for cancer, metabolic disorders, and infectious diseases. The integration of CRISPR-based models, advanced imaging, and multi-omics approaches continues to unravel the complex regulation of this process. Targeting LCFA transport proteins holds promise for therapeutic intervention, and ongoing research will likely uncover new layers of regulation and disease connections.
References
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- 3. Dutta-Roy AK. 2000. Cellular uptake of long-chain fatty acids: role of membrane-associated fatty-acid-binding/transport proteins.. Cell Mol Life Sci 57(10):1360-72 PMID: 11078015
- 4. Zhang L et al.. 2021. Increasing Long-Chain Dicarboxylic Acid Production in Candida tropicalis by Engineering Fatty Transporters.. Mol Biotechnol 63(6):544-555 PMID: 33786739
- 5. Tong K et al.. 2025. Long chain fatty acid transport via SLC27A1 enhances DAG-3-P synthesis and accelerates colorectal cancer metastasis.. Sci Rep 15(1):31937 PMID: 40883416
- 6. Jackson M et al.. 2007. Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium tuberculosis: biosynthesis, transport, regulation and biological activities.. Tuberculosis (Edinb) 87(2):78-86 PMID: 17030019
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