GO:0046942 carboxylic acid transport: Cellular Metabolism Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0046942 carboxylic acid transport describes the directed movement of carboxylic acids (organic acids containing one or more carboxyl groups) across cellular membranes or between cells, mediated by transporters or pores [1,3].
• Carboxylic acid transporters are critical for nutrient uptake, metabolic waste removal, and drug resistance in pathogens such as Candida species and Mycobacterium tuberculosis [1,5].
• In mammals, monocarboxylate transporters (MCTs) facilitate the uptake of succinate into brown adipocytes, linking carboxylic acid transport to thermogenesis and metabolic regulation.
• Plant carboxylic acid transporters, such as PIN-FORMED auxin transporters, mediate the transport of auxin and phenoxyacetic acid herbicides, affecting growth and herbicide efficacy.
• Dysregulation of carboxylic acid transport is implicated in cancer metabolism, neurodegeneration, and infectious diseases, making these transporters attractive drug targets [2,5].
• CRISPR-based knockout, knock-in, and overexpression models enable precise functional dissection of carboxylic acid transporters in health and disease [1,6].
Description
Carboxylic acid transport (GO:0046942) is a fundamental biological process that governs the movement of carboxylic acids—organic acids containing one or more carboxyl (COOH) groups or their anions (COO-)—across cellular membranes or between cells [1,3]. This process is mediated by specialized transporter proteins or pores that facilitate the directed movement of these molecules, which include key metabolites such as lactate, pyruvate, succinate, malate, and citrate [2,4]. Carboxylic acid transporters are essential for maintaining metabolic homeostasis, enabling cells to import nutrients and export waste products. In pathogenic microorganisms, these transporters contribute to virulence and drug resistance, as seen in Candida species and Mycobacterium tuberculosis [1,5]. In plants, they regulate growth and development by transporting auxin and other signaling molecules [7,8]. In mammals, carboxylic acid transport is critical for energy metabolism, particularly in tissues such as brown adipose tissue, where succinate uptake via monocarboxylate transporters supports thermogenesis. Given their broad physiological roles, carboxylic acid transporters are emerging as promising targets for therapeutic intervention in cancer, metabolic disorders, and infectious diseases [2,5]. Understanding the molecular mechanisms, regulation, and disease relevance of carboxylic acid transport is therefore of high research priority [1,6].
carboxylic acid transport At A Glance
| GO ID | GO:0046942 |
|---|---|
| GO term | carboxylic acid transport |
| Ontology | biological_process |
| Synonym | none |
| Major function | Directed movement of carboxylic acids across membranes or between cells via transporters or pores |
| Substrates | Carboxylic acids such as lactate, pyruvate, succinate, malate, citrate, and auxin |
| Cellular locations | Plasma membrane, mitochondrial membrane, vacuolar membrane |
| Representative transporters | MCTs (monocarboxylate transporters), MmpL3, PIN-FORMED proteins, Jen1, Ady2 |
| Associated diseases | Cancer, tuberculosis, candidiasis, metabolic disorders |
What Is GO:0046942?
GO:0046942 carboxylic acid transport is defined as the directed movement of carboxylic acids into, out of, or within a cell, or between cells, by means of some agent such as a transporter or pore. Carboxylic acids are organic acids containing one or more carboxyl (COOH) groups or anions (COO-). This process encompasses the translocation of these molecules across biological membranes, often against a concentration gradient, and is mediated by specific transport proteins [1,3].
Why Is carboxylic acid transport Important in Cell Biology?
Carboxylic acid transport is essential for cellular metabolism, nutrient acquisition, and waste elimination across all domains of life [1,3]. In humans, it supports energy homeostasis and is linked to cancer and metabolic diseases. In pathogens, it contributes to virulence and drug resistance, making it a target for anti-infective therapies [1,5]. In plants, it regulates growth and herbicide sensitivity. Thus, understanding this process has broad implications for basic biology, medicine, and agriculture.
• Enables uptake of key metabolites like lactate and succinate for energy production.
• Facilitates secretion of metabolic waste products such as acetate and lactate.
• Critical for virulence in fungal pathogens like Candida albicans.
• Essential for Mycobacterium tuberculosis survival via MmpL3-mediated transport.
• Regulates plant growth and development through auxin transport [7,8].
• Involved in herbicide uptake and efficacy in crops.
• Linked to cancer metabolism and tumor microenvironment acidification.
• Potential target for anti-obesity and anti-diabetic therapies via brown adipocyte activation.
• Mediates drug resistance in yeast by exporting antifungal agents.
• Provides a model for studying membrane transport mechanisms and evolution [3,4].
What Happens During carboxylic acid transport?
Substrate Recognition and Binding
In simple terms: The transporter first recognizes and grabs the carboxylic acid molecule.
Carboxylic acid transporters exhibit specificity for substrates based on molecular size, charge, and functional groups. For example, the yeast Jen1 transporter recognizes lactate, pyruvate, and other short-chain monocarboxylates. In Candida utilis, a general organic acid permease transports L-malic acid and other short-chain carboxylic acids. Substrate binding typically involves protonation of the carboxyl group, allowing the neutral acid form to enter the binding pocket. Structural studies of MmpL3 in Mycobacterium tuberculosis reveal a large substrate-binding cavity that accommodates trehalose monomycolate, a carboxylic acid-containing lipid.
Conformational Change and Translocation
In simple terms: The transporter changes shape to move the molecule across the membrane.
Upon substrate binding, transporters undergo conformational changes that shuttle the carboxylic acid across the lipid bilayer. Monocarboxylate transporters (MCTs) utilize a proton-coupled symport mechanism, where the proton gradient drives substrate translocation. In brown adipocytes, MCTs facilitate succinate uptake, which is then oxidized to support thermogenesis. The MmpL3 transporter in M. tuberculosis uses the proton motive force to export trehalose monomycolate, a process essential for cell wall biosynthesis. Plant PIN-FORMED auxin transporters mediate the efflux of auxin (indole-3-acetic acid), a carboxylic acid hormone, through a similar conformational cycling mechanism.
Substrate Release and Recycling
In simple terms: The molecule is released on the other side, and the transporter resets.
After translocation, the carboxylic acid is released into the cytoplasm or extracellular space, and the transporter returns to its original conformation. In yeast, the Jen1 transporter is internalized and degraded in response to glucose, a process regulated by ubiquitination. In Candida species, carboxylic acid transporters are regulated by environmental pH and nutrient availability, ensuring efficient substrate uptake. The release step is often coupled to proton symport, as seen in MCTs, where the proton is also released, completing the cycle.
Regulation and Cellular Integration
In simple terms: The cell controls when and how much transport happens.
Carboxylic acid transport is tightly regulated at transcriptional, post-transcriptional, and post-translational levels. In yeasts, the expression of carboxylic acid transporters is induced by the presence of substrates and repressed by glucose. In Candida albicans, transporter genes are upregulated during infection, contributing to virulence. In mammals, MCT expression is regulated by hypoxia-inducible factor 1 (HIF-1) and metabolic demands. Plant PIN-FORMED auxin transporters are regulated by phosphorylation and vesicle trafficking, affecting auxin distribution and plant development [7,8].
Physiological Consequences
In simple terms: Transport affects the whole organism's health and function.
Carboxylic acid transport impacts diverse physiological processes. In brown adipocytes, succinate uptake via MCTs enhances thermogenesis and energy expenditure. In M. tuberculosis, MmpL3-mediated transport is essential for cell wall integrity and survival, making it a drug target. In plants, auxin transport regulates growth, development, and responses to herbicides like phenoxyacetic acid. In pathogenic fungi, carboxylic acid transporters contribute to nutrient acquisition and drug resistance [1,6].
Key Genes Involved in GO:0046942 carboxylic acid transport
The following genes encode transporters and regulators involved in carboxylic acid transport across various organisms.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC16A1 (MCT1) | Monocarboxylate transporter 1; facilitates lactate, pyruvate, and succinate transport | Cancer metabolism, brown adipocyte thermogenesis |
| SLC16A3 (MCT4) | Monocarboxylate transporter 4; exports lactate from glycolytic cells | Tumor microenvironment acidification, cancer progression |
| MmpL3 | Mycobacterial membrane protein large 3; exports trehalose monomycolate | Anti-tuberculosis drug target |
| JEN1 | Yeast monocarboxylate transporter; uptakes lactate, pyruvate | Fungal metabolism, glucose repression |
| ADY2 | Yeast acetate transporter; mediates acetic acid uptake | Acetate metabolism, Candida virulence |
| PIN1 | Plant auxin efflux carrier; transports indole-3-acetic acid | Plant development, herbicide transport |
| PIN2 | Plant auxin efflux carrier; root gravitropism | Auxin distribution, herbicide sensitivity |
| PIN3 | Plant auxin efflux carrier; lateral root development | Auxin transport, phenoxyacetic acid herbicides |
| PIN4 | Plant auxin efflux carrier; embryo patterning | Auxin transport, herbicide efficacy |
| PIN7 | Plant auxin efflux carrier; vascular development | Auxin transport, herbicide efficacy |
| PDR12 | Yeast ABC transporter; exports weak acids | Antifungal resistance, Candida pathogenesis |
| AZR1 | Yeast transporter; exports acetic acid | Acetic acid resistance, Candida virulence |
| GPR1 | Yeast G-protein coupled receptor; senses carboxylic acids | Fungal metabolism, virulence |
| HGT1 | Yeast glucose transporter; also transports carboxylic acids | Nutrient uptake, Candida pathogenesis |
| SLN1 | Yeast histidine kinase; regulates carboxylic acid transport | Stress response, Candida virulence |
| MCT7 | Monocarboxylate transporter 7; transports succinate | Brown adipocyte thermogenesis |
| MCT9 | Monocarboxylate transporter 9; transports succinate | Brown adipocyte thermogenesis |
How Is carboxylic acid transport Regulated?
Carboxylic acid transport is regulated at multiple levels. In yeasts, transporter genes are induced by their substrates and repressed by glucose, a phenomenon known as glucose repression. In Candida albicans, transporter expression is upregulated during infection and in response to environmental pH changes. In mammals, MCT expression is regulated by hypoxia-inducible factor 1 (HIF-1) and metabolic demands. Plant PIN-FORMED auxin transporters are regulated by phosphorylation and vesicle trafficking, affecting auxin distribution and plant development [7,8]. Additionally, post-translational modifications such as ubiquitination control transporter stability and localization.
carboxylic acid transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC16A1 (MCT1) | Cancer metabolism, lactate transport | Knockout in cancer cell lines, xenograft models |
| MmpL3 | Tuberculosis | Knockout in Mycobacterium tuberculosis, infection models |
| JEN1 | Candidiasis, fungal metabolism | Knockout in Candida albicans, virulence assays |
| PIN1 | Plant development, herbicide response | Knockout in Arabidopsis thaliana, herbicide sensitivity assays |
| SLC16A7 (MCT2) | Neurodegeneration, lactate transport | Knockout in neurons, neurodegeneration models |
Carboxylic Acid Transport in Cancer
Cancer cells often exhibit altered carboxylic acid transport to support rapid growth and survival. Monocarboxylate transporters (MCTs) such as MCT1 and MCT4 are upregulated in many tumors, facilitating lactate export and import to maintain glycolytic metabolism and acidify the tumor microenvironment. This adaptation promotes invasion, metastasis, and resistance to therapy. Targeting MCTs has emerged as a potential anticancer strategy.
Carboxylic Acid Transport in Infectious Diseases
In Mycobacterium tuberculosis, the MmpL3 transporter is essential for cell wall biosynthesis and virulence, making it a validated drug target. In Candida species, carboxylic acid transporters contribute to nutrient acquisition, drug resistance, and pathogenesis. For example, the acetate transporter Ady2 and the ABC transporter PDR12 are involved in acetic acid resistance and antifungal tolerance. Inhibiting these transporters could reduce fungal virulence and overcome resistance.
Carboxylic Acid Transport in Metabolic Disorders
In brown adipocytes, monocarboxylate transporters facilitate succinate uptake, which enhances thermogenesis and energy expenditure. Dysregulation of this process may contribute to obesity and metabolic syndrome. Modulating carboxylic acid transport in adipose tissue could offer therapeutic benefits for metabolic disorders.
Carboxylic Acid Transport in Plants and Herbicide Action
Plant PIN-FORMED auxin transporters mediate the transport of auxin and phenoxyacetic acid herbicides, affecting growth and herbicide efficacy. Understanding these transporters can inform agricultural practices and the development of herbicide-resistant crops [7,8].
From carboxylic acid transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does SLC16A1 knockout reduce lactate uptake in cancer cells? | CRISPR knockout in HeLa or MCF7 cells |
| Does MmpL3 point mutation confer drug resistance? | CRISPR point mutation in Mycobacterium tuberculosis |
| Can MCT4 overexpression enhance lactate export? | CRISPR overexpression in cancer cell lines |
| Does JEN1 knockout affect Candida virulence? | CRISPR knockout in Candida albicans, mouse infection model |
| Does PIN1 knock-in alter auxin transport? | CRISPR knock-in in Arabidopsis thaliana |
| Can tagged MCT1 be used for live-cell imaging? | CRISPR tagged knock-in in mammalian cells |
How to Study the carboxylic acid transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Gene function loss | Assessing transporter necessity in metabolism |
| RNA interference | Gene knockdown | Transient silencing of transporter genes |
| Radiolabeled transport assay | Substrate uptake rate | Quantifying transport kinetics |
| Cryo-EM | Protein structure | Determining transporter conformation |
| RNA-seq | Gene expression | Identifying regulated transporters |
| Proteomics | Protein abundance | Validating transporter expression |
| Live-cell imaging | Substrate localization | Tracking transport in real time |
Genetic Knockout and Knockdown
CRISPR-Cas9 knockout and RNA interference are widely used to disrupt carboxylic acid transporter genes and assess their function. For example, knockout of SLC16A1 in cancer cells reduces lactate uptake and alters metabolism. In Candida albicans, JEN1 knockout impairs growth on lactate and reduces virulence.
Transport Assays
Radiolabeled or fluorescent carboxylic acid substrates are used to measure transport activity in cells or vesicles. For instance, uptake of 14C-labeled succinate in brown adipocytes can be quantified to assess MCT function. In yeast, transport assays with 14C-lactate or 14C-malate reveal transporter specificity [3,4].
Structural Biology
X-ray crystallography and cryo-electron microscopy provide high-resolution structures of carboxylic acid transporters, revealing substrate-binding sites and conformational changes. The structure of MmpL3 has been solved, aiding drug design.
Transcriptomics and Proteomics
RNA-seq and proteomics can identify transporters differentially expressed under various conditions. In Candida albicans, transcriptomic profiling during infection reveals upregulated carboxylic acid transporters. In plants, proteomic analysis of PIN proteins provides insights into their regulation.
How CRISPR Can Be Used to Study GO:0046942 carboxylic acid transport
Knockout
CRISPR knockout is used to completely ablate carboxylic acid transporter genes, enabling loss-of-function studies. For example, SLC16A1 knockout in cancer cells reduces lactate uptake and inhibits tumor growth. In Candida albicans, JEN1 knockout attenuates virulence in mouse models.
Point Mutation
CRISPR point mutation introduces specific amino acid substitutions to study transporter function or drug resistance. For instance, mutations in MmpL3 can confer resistance to anti-tuberculosis drugs, and CRISPR can recreate these mutations to validate their role.
Knock-in
CRISPR knock-in allows the insertion of tags or reporter genes into endogenous transporter loci. Tagged MCT1 can be used for live-cell imaging to track localization and dynamics. In plants, knock-in of fluorescent tags on PIN proteins enables visualization of auxin transport.
Overexpression
CRISPR activation (CRISPRa) or cDNA overexpression is used to increase transporter expression, enabling gain-of-function studies. Overexpression of MCT4 in cancer cells enhances lactate export and acidifies the microenvironment. In yeast, overexpression of JEN1 increases lactate uptake.
How EDITGENE Supports carboxylic acid transport Research
Researchers studying carboxylic acid transport-related genes often need to determine whether a candidate gene is causally involved in substrate uptake, metabolism, or disease. EDITGENE provides comprehensive CRISPR services to generate precise cellular and animal models for functional validation.
Contact EDITGENE today to design your custom CRISPR model for carboxylic acid transport research.
Frequently Asked Questions About carboxylic acid transport
What is carboxylic acid transport?
Carboxylic acid transport (GO:0046942) is the directed movement of carboxylic acids into, out of, or within a cell, or between cells, mediated by transporters or pores [1,3].
What genes are involved in carboxylic acid transport?
Key genes include SLC16A1 (MCT1), SLC16A3 (MCT4), MmpL3, JEN1, ADY2, and PIN-FORMED auxin transporters [1,2,5,7].
How is carboxylic acid transport regulated?
It is regulated by substrate availability, glucose repression, pH, hypoxia, and post-translational modifications [1,3,2].
What diseases are associated with carboxylic acid transport?
Cancer, tuberculosis, candidiasis, metabolic disorders, and neurodegeneration [1,2,5].
What is the role of MCTs in cancer?
MCTs facilitate lactate transport, supporting tumor metabolism and acidification of the microenvironment.
How can I study carboxylic acid transport using CRISPR?
CRISPR knockout, knock-in, point mutation, and overexpression models enable functional studies of transporters [1,6].
What is MmpL3 and why is it important?
MmpL3 is a mycobacterial transporter essential for cell wall biosynthesis and a target for anti-tuberculosis drugs.
Do plants have carboxylic acid transporters?
Yes, PIN-FORMED auxin transporters mediate auxin and herbicide transport in plants [7,8].
What methods measure carboxylic acid transport?
Radiolabeled transport assays, live-cell imaging, and electrophysiology [2,3].
Can carboxylic acid transport be targeted therapeutically?
Yes, inhibitors of MCTs and MmpL3 are under development for cancer and tuberculosis [2,5].
Conclusion
Carboxylic acid transport (GO:0046942) is a fundamental biological process with broad implications for metabolism, pathogenesis, and plant physiology. Understanding its molecular mechanisms and regulation offers opportunities for therapeutic intervention in cancer, infectious diseases, and metabolic disorders. CRISPR-based models are invaluable for dissecting transporter function and validating drug targets.
References
- 1. Alves R et al.. 2020. Carboxylic Acid Transporters in Candida Pathogenesis.. mBio 11(3) PMID: 32398310
- 2. Reddy A et al.. 2024. Monocarboxylate transporters facilitate succinate uptake into brown adipocytes.. Nat Metab 6(3):567-577 PMID: 38378996
- 3. Casal M et al.. 2008. Transport of carboxylic acids in yeasts.. FEMS Microbiol Rev 32(6):974-94 PMID: 18759742
- 4. Cássio F et al.. 1993. A comparative study on the transport of L(-)malic acid and other short-chain carboxylic acids in the yeast Candida utilis: evidence for a general organic acid permease.. Yeast 9(7):743-52 PMID: 8368008
- 5. Bolla JR. 2020. Targeting MmpL3 for anti-tuberculosis drug development.. Biochem Soc Trans 48(4):1463-1472 PMID: 32662825
- 6. Wu T et al.. 2023. Fungal carboxylate transporters: recent manipulations and applications.. Appl Microbiol Biotechnol 107(19):5909-5922 PMID: 37561180
- 7. Schulz L et al.. 2025. Transport of phenoxyacetic acid herbicides by PIN-FORMED auxin transporters.. Nat Plants 11(5):1049-1059 PMID: 40263580
- 8. Boursiac Y et al.. 2013. ABA transport and transporters.. Trends Plant Sci 18(6):325-33 PMID: 23453706
