GO:0015141 succinate transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015141 describes the molecular function of moving succinate (the dianion of ethane dicarboxylic acid) across a membrane.
• This activity is often part of sodium-coupled or antiporter systems that also handle other Krebs cycle intermediates such as fumarate and malate.
• The term is distinct from succinate dehydrogenase or succinate:quinone oxidoreductase, which catalyze redox reactions rather than transport.
• Succinate transport influences mitochondrial metabolism, immune signaling, and airway hydration, making it relevant to inflammatory diseases and cystic fibrosis.
• Key proteins include SLC13A1 and related SLC13 family members, as well as bacterial succinate:menaquinone oxidoreductases that interact with transport processes.
• Experimental approaches range from solid-state NMR of membrane proteins to CRISPR knockout and overexpression models for functional validation.
Description
Succinate transmembrane transporter activity (GO:0015141) is a molecular function that enables the transfer of succinate, the dianion of ethane dicarboxylic acid, from one side of a membrane to the other. This activity is fundamental to cellular metabolism because succinate is a key intermediate of the tricarboxylic acid (TCA) cycle and also acts as a signaling molecule in various physiological contexts. Researchers study this term to understand how cells and organelles maintain metabolic homeostasis, how bacteria energize their membranes, and how defects in succinate handling contribute to disease. The QuickGO definition emphasizes the directional transport of succinate across a lipid bilayer, which distinguishes it from enzymatic activities that modify succinate. In eukaryotes, sodium-coupled transporters for Krebs cycle intermediates, such as those in the SLC13 family, mediate succinate uptake or efflux, often in exchange for other dicarboxylates like fumarate or malate. In bacteria, succinate transport is linked to respiratory chains and energy conservation, as seen in Bacillus subtilis and Paracoccus denitrificans. Understanding GO:0015141 therefore bridges membrane biology, metabolism, and immunology, with implications for diseases ranging from cystic fibrosis to inflammatory disorders.
succinate transmembrane transporter activity At A Glance
| GO ID | GO:0015141 |
|---|---|
| GO term | succinate transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | dicarboxylate (succinate/fumarate/malate) antiporter activity |
| Major function | Transfer of succinate across a membrane |
| Definition source | QuickGO |
| Related processes | TCA cycle, mitochondrial metabolism, bacterial respiration, immune signaling |
| Example proteins | SLC13A1, succinate:menaquinone oxidoreductase components |
What Is GO:0015141?
GO:0015141, succinate transmembrane transporter activity, is defined as enabling the transfer of succinate, the dianion of ethane dicarboxylic acid, from one side of a membrane to the other. This function is typically mediated by integral membrane proteins that form a channel or carrier to move succinate across biological membranes, often coupled to the movement of other ions or metabolites. The synonym dicarboxylate (succinate/fumarate/malate) antiporter activity highlights that some transporters can exchange succinate with other dicarboxylates.
Why Is succinate transmembrane transporter activity Important in Cell Biology?
Succinate transmembrane transporter activity is critical for cellular energy metabolism and signaling because succinate must be moved between compartments to feed the TCA cycle and to act as an extracellular messenger. Dysregulation of succinate transport can alter mitochondrial function, immune responses, and airway surface liquid homeostasis, as shown in studies of cystic fibrosis and inflammatory diseases. In bacteria, succinate transport supports membrane energization and respiratory chain activity, which are targets for antimicrobial research. Thus, understanding GO:0015141 provides mechanistic insight into both normal physiology and disease states.
• Maintains TCA cycle flux by moving succinate across mitochondrial and plasma membranes.
• Supports bacterial respiration and energy conservation via succinate:quinone oxidoreductase-linked transport.
• Modulates immune cell function through succinate signaling in inflammation.
• Contributes to airway hydration and mucociliary clearance, with implications for cystic fibrosis.
• Provides a target for studying metabolic reprogramming in cancer and immune disorders.
• Enables sodium-coupled transport of Krebs cycle intermediates in epithelial tissues.
• Influences mitochondrial reactive oxygen species production and cellular redox balance.
• Serves as a model for membrane protein structure-function studies using solid-state NMR.
• Links metabolism to gene regulation via succinate as a signaling molecule.
• Offers potential therapeutic entry points for diseases of succinate accumulation.
Molecular Mechanism of succinate transmembrane transporter activity
Substrate recognition and binding
In simple terms: The transporter first grabs succinate from one side of the membrane.
Transporters with succinate transmembrane transporter activity recognize succinate, the dianion of ethane dicarboxylic acid, through specific binding sites that discriminate it from other dicarboxylates. Sodium-coupled transporters for Krebs cycle intermediates, such as those in the SLC13 family, use sodium gradients to drive substrate binding and translocation. The synonym dicarboxylate (succinate/fumarate/malate) antiporter activity indicates that some transporters can bind multiple dicarboxylates and exchange them.
Conformational change and translocation
In simple terms: The protein changes shape to move succinate across the membrane.
After binding, the transporter undergoes conformational changes that expose succinate to the opposite side of the membrane. In sodium-coupled transporters, this process is energized by the sodium electrochemical gradient, allowing succinate to move against its concentration gradient. Solid-state NMR studies of membrane proteins in lipid bilayers have provided insights into such conformational dynamics.
Coupling to other ions or metabolites
In simple terms: Succinate movement is often tied to the movement of another molecule.
Many succinate transporters function as antiporters, exchanging succinate for fumarate or malate, as reflected in the synonym dicarboxylate (succinate/fumarate/malate) antiporter activity. Sodium-coupled transporters use sodium influx to drive succinate uptake, linking transport to cellular ion homeostasis. In bacteria, succinate transport can be coupled to menaquinone reduction via succinate:menaquinone oxidoreductase, which energizes the membrane.
Regulation by membrane potential and lipid environment
In simple terms: The surrounding membrane and electrical charge affect how well the transporter works.
The activity of succinate transporters is influenced by the membrane potential and lipid composition, as shown for bacterial membrane vesicles where energization increases catalytic activity of succinate:menaquinone oxidoreductase. Solid-state NMR studies highlight the importance of lipid bilayers in maintaining the functional conformation of membrane proteins. Allosteric regulation by transmembrane polar relays has been described for other transporters, suggesting similar mechanisms may apply.
Key Genes Involved in GO:0015141 succinate transmembrane transporter activity
The following genes and proteins are associated with succinate transmembrane transporter activity or related transport processes, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC13A1 | Sodium-coupled sulfate/dicarboxylate transporter | Model for sodium-coupled transport of Krebs cycle intermediates |
| SLC13A2 | Sodium-coupled dicarboxylate transporter | Studied for succinate and citrate transport in kidney and intestine |
| SLC13A3 | Sodium-coupled dicarboxylate transporter | Involved in succinate transport in liver and brain |
| SLC13A5 | Sodium-coupled citrate transporter | Related to dicarboxylate transport family |
| SDHA | Succinate dehydrogenase subunit A | Links succinate oxidation to respiratory chain, not transport per se |
| SDHB | Succinate dehydrogenase subunit B | Component of complex II, often studied with succinate metabolism |
| SDHC | Succinate dehydrogenase subunit C | Membrane anchor of complex II, relevant to succinate:quinone oxidoreductase |
| SDHD | Succinate dehydrogenase subunit D | Membrane subunit of complex II, involved in succinate oxidation |
| IRG1 | Itaconate production from cis-aconitate | Links succinate metabolism to immunometabolism |
| CFTR | Chloride channel | Succinate chemosensing induces CFTR-dependent airway clearance |
| SUCNR1 | Succinate receptor | Mediates succinate signaling in inflammation |
| MCT1 | Monocarboxylate transporter | Can transport succinate in some contexts |
| MCT4 | Monocarboxylate transporter | Related to dicarboxylate transport |
| OAT1 | Organic anion transporter | Contributes to succinate transport in kidney |
| OAT3 | Organic anion transporter | Involved in succinate handling |
| ABCG5 | Sterol transporter | Model for transmembrane polar relay allostery |
| ABCG8 | Sterol transporter | Similar to ABCG5, provides mechanistic parallels |
How Is succinate transmembrane transporter activity Regulated?
Succinate transmembrane transporter activity is regulated at multiple levels. Sodium-coupled transporters depend on the sodium gradient maintained by Na+/K+-ATPase, so changes in cellular energy status affect transport rates. In bacteria, membrane energization increases the catalytic activity of succinate:menaquinone oxidoreductase, indicating that the proton motive force regulates succinate handling. Allosteric regulation via transmembrane polar relays has been described for ABCG5/G8 sterol transporters, suggesting a general mechanism for membrane transporter control. Additionally, succinate levels themselves can influence signaling through SUCNR1 and immunometabolic pathways involving IRG1 and itaconate.
succinate transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CFTR | Cystic fibrosis, airway clearance | CFTR knockout or knock-in cell models |
| IRG1 | Inflammatory diseases, immunometabolism | IRG1 knockout macrophages |
| SDHA | SDH-deficient tumors | SDHA knockout cell lines |
| SLC13A1 | Metabolic disorders, sulfate transport | SLC13A1 overexpression or knockout |
| SUCNR1 | Inflammation, metabolic sensing | SUCNR1 knockout mice or cells |
Cystic fibrosis and airway clearance
Succinate chemosensing induces CFTR-dependent airway clearance, and this process is impaired in cystic fibrosis. This links succinate transport and signaling to mucociliary clearance and lung health, suggesting that modulators of succinate transmembrane transporter activity could influence airway hydration.
Inflammatory diseases and immunometabolism
The IRG1-itaconate axis connects succinate metabolism to immunometabolism, with mechanistic roles in inflammatory diseases. Succinate transport across membranes affects intracellular succinate levels, which in turn influence itaconate production and immune cell function.
Cancer and metabolic reprogramming
Altered succinate handling is observed in cancers with mutations in succinate dehydrogenase, leading to succinate accumulation and oncogenic signaling. Although transport is distinct from oxidation, the two processes are functionally linked, and transporters may contribute to succinate flux in tumors.
From succinate transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC13A1 affect succinate uptake? | SLC13A1 knockout cell line |
| Can a point mutation alter substrate specificity? | Point-mutation knock-in of SLC13A1 |
| Does tagging affect transporter localization? | Tagged knock-in of SLC13A1 |
| Does overexpression increase succinate transport? | SLC13A1 overexpression stable line |
| Is CFTR-dependent airway clearance succinate-sensitive? | CFTR knockout or knock-in airway epithelial cells |
| Does IRG1 modulate succinate transport? | IRG1 knockout macrophages |
How to Study the succinate transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled succinate uptake | Transport rate | Functional characterization of transporters |
| Solid-state NMR | Protein structure and dynamics | Membrane protein conformational studies |
| Membrane potential assay | Energization state | Bacterial succinate oxidation |
| CRISPR knockout screen | Gene essentiality or modifiers | Identifying regulators of succinate transport |
| RNA-seq | Gene expression changes | Response to succinate transport modulation |
| Proteomics | Protein abundance and interactions | Identifying transporter complexes |
| Imaging of airway surface liquid | Mucociliary clearance | CFTR-dependent succinate chemosensing |
| Metabolomics | Succinate and related metabolites | Measuring flux through transport pathways |
Transport assays with radiolabeled succinate
Uptake or efflux of radiolabeled succinate in membrane vesicles or cells can directly measure succinate transmembrane transporter activity. Such assays are often performed with sodium gradients to assess sodium-coupled transport.
Solid-state NMR of membrane proteins
Solid-state NMR in lipid bilayers provides structural and dynamic information on membrane transporters, including those involved in succinate transport. This method helps resolve conformational changes during transport.
Electrophysiology and membrane potential measurements
Membrane energization can be monitored to assess the impact of succinate transport on bacterial membrane potential, as shown for Bacillus subtilis membrane vesicles. This approach links transport activity to respiratory chain function.
CRISPR-based genetic screens
CRISPR knockout or activation screens can identify genes that regulate succinate transport and signaling, including SLC13 family members and CFTR. These screens are useful for discovering modifiers of succinate-dependent phenotypes.
How CRISPR Can Be Used to Study GO:0015141 succinate transmembrane transporter activity
Knockout
CRISPR knockout of SLC13A1 or related transporters can abolish succinate transport, allowing researchers to test its role in metabolism and signaling. Knockout of CFTR impairs succinate-induced airway clearance, providing a disease-relevant model.
Point Mutation
Point mutations in transporter genes can alter substrate specificity or coupling to sodium, as studied for sodium-coupled transporters. Such models help dissect the molecular determinants of succinate recognition.
Knock-in
Knock-in of tagged transporters enables localization and interaction studies in native contexts. Tagged knock-in of SLC13A1 can reveal trafficking and membrane insertion dynamics.
Overexpression
Overexpression of succinate transporters increases transport capacity and can amplify downstream signaling, such as succinate-induced CFTR-dependent clearance. This approach is useful for biochemical and structural studies.
How EDITGENE Supports succinate transmembrane transporter activity Research
Researchers studying succinate transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in succinate transport, signaling, or disease phenotypes. EDITGENE provides CRISPR-based cell models and screening services to accelerate this discovery process.
Contact EDITGENE today to design your custom CRISPR model for succinate transmembrane transporter activity research.
Frequently Asked Questions About succinate transmembrane transporter activity
What is succinate transmembrane transporter activity?
It is a molecular function (GO:0015141) that enables the transfer of succinate, the dianion of ethane dicarboxylic acid, from one side of a membrane to the other.
What genes are involved in succinate transmembrane transporter activity?
Genes such as SLC13A1, SLC13A2, SLC13A3, and other sodium-coupled transporters for Krebs cycle intermediates are involved.
What is the synonym for GO:0015141?
The synonym is dicarboxylate (succinate/fumarate/malate) antiporter activity.
How is succinate transport regulated?
It is regulated by sodium gradients, membrane potential, and allosteric mechanisms, as seen in sodium-coupled transporters and bacterial systems.
What diseases are linked to succinate transport?
Cystic fibrosis, inflammatory diseases, and cancers with succinate dehydrogenase mutations are linked to succinate transport and metabolism.
What methods study succinate transmembrane transporter activity?
Radiolabeled uptake assays, solid-state NMR, membrane potential measurements, and CRISPR screens are commonly used.
Is succinate transmembrane transporter activity the same as succinate dehydrogenase?
No, succinate dehydrogenase catalyzes the oxidation of succinate, while GO:0015141 is about moving succinate across membranes.
Can CRISPR be used to study succinate transporters?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools for dissecting transporter function.
What is the role of succinate transport in bacteria?
In bacteria, succinate transport is coupled to menaquinone reduction and membrane energization, supporting respiration.
How does succinate transport affect airway clearance?
Succinate chemosensing induces CFTR-dependent airway clearance, which is impaired in cystic fibrosis.
Conclusion
Succinate transmembrane transporter activity (GO:0015141) is a fundamental molecular function that bridges metabolism, signaling, and membrane biology. Its study is facilitated by diverse experimental approaches, from radiolabeled transport assays to CRISPR-based genetic models. Understanding this activity has implications for diseases such as cystic fibrosis, inflammatory disorders, and cancer, making it a valuable target for both basic and translational research.
References
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- 2. Apablaza T et al.. 2025. Succinate Chemosensing Induces Cystic Fibrosis Transmembrane Conductance Regulator-dependent Airway Clearance that Is Impaired in Cystic Fibrosis.. Am J Respir Cell Mol Biol 73(5):769-779 PMID: 40239014
- 3. Xavier BM et al.. 2020. Transmembrane Polar Relay Drives the Allosteric Regulation for ABCG5/G8 Sterol Transporter.. Int J Mol Sci 21(22) PMID: 33228147
- 4. Pajor AM. 1999. Sodium-coupled transporters for Krebs cycle intermediates.. Annu Rev Physiol 61:663-82 PMID: 10099705
- 5. Liu Y et al.. 2026. IRG1-itaconate axis in immunometabolism: mechanistic roles and therapeutic potential in inflammatory diseases.. Front Immunol 17:1767601 PMID: 41743716
- 6. Azarkina NV et al.. 2010. Energization of Bacillus subtilis membrane vesicles increases catalytic activity of succinate:menaquinone oxidoreductase.. Biochemistry (Mosc) 75(1):50-62 PMID: 20331424
- 7. Hederstedt L. 2002. Succinate:quinone oxidoreductase in the bacteria Paracoccus denitrificans and Bacillus subtilis.. Biochim Biophys Acta 1553(1-2):74-83 PMID: 11803018
- 8. Gopinath T et al.. 2021. Solid-State NMR of Membrane Proteins in Lipid Bilayers: To Spin or Not To Spin?. Acc Chem Res 54(6):1430-1439 PMID: 33655754
