GO:0071422 succinate transmembrane transport: Transport Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071422 succinate transmembrane transport is the biological process that moves the Krebs cycle intermediate succinate across biological membranes.
• Succinate transport is mediated by sodium-coupled transporters such as SLC13A1 and by mitochondrial respiratory chain complexes that handle succinate at the inner membrane.
• Succinate transport is central to mitochondrial energy metabolism and to the redox balance of respiratory complex II, which oxidizes succinate to fumarate.
• Pharmacological inhibition of succinate transport, for example by valproate, can disrupt mitochondrial function in kidney and other tissues.
• Succinate chemosensing and transport influence airway clearance and are impaired in cystic fibrosis, linking this process to epithelial physiology.
• Assays for succinate transport and oxidative phosphorylation are used to discover inhibitors of mycobacterial and mitochondrial energy metabolism.
Description
Succinate is a central intermediate of the tricarboxylic acid (TCA) cycle and a signaling molecule, and its movement across membranes is essential for mitochondrial energy production and cellular metabolism. The Gene Ontology term GO:0071422, succinate transmembrane transport, describes the process in which succinate is transported across a membrane. This process is carried out by dedicated transport proteins and by respiratory chain complexes that couple succinate handling to electron transfer. Understanding succinate transmembrane transport is important because it connects cytosolic and mitochondrial pools of succinate and influences pathways ranging from oxidative phosphorylation to inflammation and fibrosis.
succinate transmembrane transport At A Glance
| GO ID | GO:0071422 |
|---|---|
| GO term | succinate transmembrane transport |
| Ontology | biological_process |
| Synonym | succinate membrane transport; transmembrane succinate transport |
| Definition | The process in which succinate is transported across a membrane. |
| Major function | Movement of succinate across biological membranes to support mitochondrial energy metabolism and cellular signaling. |
| Key transporters | SLC13A1 (Na+-sulfate/succinate cotransporter) and mitochondrial respiratory chain complexes. |
| Related process | Oxidative phosphorylation and TCA cycle metabolism. |
| Disease relevance | Cystic fibrosis airway clearance, mitochondrial dysfunction, and metabolic disorders. |
What Is GO:0071422?
GO:0071422 succinate transmembrane transport is defined as the process in which succinate is transported across a membrane. In practical terms, it covers the directed movement of the dicarboxylate succinate from one side of a lipid bilayer to the other, whether by sodium-coupled cotransport, by mitochondrial carrier proteins, or as part of respiratory complex II activity at the inner mitochondrial membrane.
Why Is succinate transmembrane transport Important in Cell Biology?
Succinate transmembrane transport is important because succinate must cross membranes to feed the mitochondrial electron transport chain and to act as a signaling molecule in different cellular compartments. Defects or pharmacological inhibition of succinate transport can impair oxidative phosphorylation, alter mitochondrial redox state, and contribute to disease phenotypes such as impaired airway clearance in cystic fibrosis. Because succinate transport is also a target in pathogens and in cancer metabolism, it is a focus for drug discovery and for understanding basic mitochondrial physiology.
• Supports mitochondrial energy production by delivering succinate to respiratory complex II.
• Maintains the TCA cycle intermediate pool across cellular compartments.
• Influences airway surface liquid and mucociliary clearance via succinate chemosensing.
• Is a pharmacological target; valproate inhibits succinate transport in renal mitochondria.
• Contributes to redox balance and reactive oxygen species production through complex II.
• Is relevant to microbial electrosynthesis and bioelectrochemical systems.
• Provides a target for inhibitors of mycobacterial oxidative phosphorylation.
• Links metabolism to inflammation and fibrosis through succinate signaling.
• Helps define substrate specificity of the SLC13 transporter family.
• Is essential for understanding mitochondrial disease mechanisms.
What Happens During succinate transmembrane transport?
Substrate recognition at the membrane
In simple terms: The transporter first recognizes succinate as its cargo.
Succinate transmembrane transport begins when a membrane protein binds succinate with sufficient affinity and specificity to distinguish it from other dicarboxylates. Sodium-coupled transporters of the SLC13 family, such as SLC13A1, recognize Krebs cycle intermediates including succinate and couple their movement to sodium gradients. This recognition step determines which metabolites enter or leave a compartment and is a key point of regulation.
Translocation across the lipid bilayer
In simple terms: The bound succinate is moved through the membrane to the other side.
After binding, the transporter undergoes conformational changes that expose succinate to the opposite side of the membrane, allowing it to be released. In mitochondria, respiratory chain complexes embedded in the inner membrane participate in succinate handling; complex II oxidizes succinate to fumarate at the matrix side while transferring electrons to the quinone pool. This coupling of transport and catalysis is central to mitochondrial energy transduction.
Coupling to ion gradients and energy state
In simple terms: Succinate movement is often powered by ion gradients.
Many succinate transporters are secondary active transporters that use the sodium gradient to drive succinate uptake. The direction and rate of transport therefore depend on the electrochemical gradient maintained by pumps such as the sodium-potassium ATPase. In mitochondria, succinate oxidation by complex II is directly linked to the proton motive force and to the redox state of the respiratory chain.
Release and metabolic integration
In simple terms: Once across, succinate enters the metabolic pathways of that compartment.
After translocation, succinate is released into the target compartment, where it can be oxidized by complex II, converted to fumarate, or act as a signaling molecule. In airway epithelia, succinate chemosensing can trigger CFTR-dependent clearance mechanisms, showing that succinate transport and sensing are integrated with epithelial function. This step connects transport to downstream physiology and disease.
Inhibition and pharmacological modulation
In simple terms: Drugs can block succinate transport.
Succinate transport can be inhibited by pharmacological agents. Valproate inhibits succinate transport in rat renal mitochondria, demonstrating that this process is druggable and can be modulated to alter mitochondrial metabolism. Assays for oxidative phosphorylation, including succinate-driven respiration, are used to identify inhibitors of mycobacterial and mitochondrial energy metabolism. Such inhibition studies help define the role of succinate transport in health and disease.
Key Genes Involved in GO:0071422 succinate transmembrane transport
The following genes and proteins are experimentally linked to succinate transmembrane transport or to the handling of succinate at membranes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC13A1 | Sodium-coupled transporter for sulfate and Krebs cycle intermediates including succinate | Model for studying Na+-dependent succinate uptake and substrate specificity |
| SDHA | Catalytic subunit of respiratory complex II that oxidizes succinate to fumarate | Target for mitochondrial metabolism and complex II assembly studies |
| SDHB | Iron-sulfur subunit of complex II involved in electron transfer from succinate | Relevant to mitochondrial disease and cancer metabolism |
| SDHC | Membrane anchor subunit of complex II | Used to study membrane insertion and complex II stability |
| SDHD | Small membrane subunit of complex II | Linked to respiratory chain assembly and oxygen sensing |
| CFTR | Chloride channel involved in airway clearance downstream of succinate chemosensing | Model for epithelial transport and cystic fibrosis research |
| SLC13A2 | Related sodium-coupled dicarboxylate transporter | Comparative studies of succinate transport specificity |
| SLC13A3 | Sodium-dependent dicarboxylate transporter | Investigation of tissue-specific succinate handling |
| SLC13A4 | Sulfate/dicarboxylate transporter family member | Family-wide analysis of transport mechanisms |
| SLC13A5 | Citrate transporter in the SLC13 family | Comparative substrate selectivity studies |
| SLC25A10 | Mitochondrial dicarboxylate carrier | Model for mitochondrial succinate exchange |
| SLC25A11 | Mitochondrial oxoglutarate/malate carrier | Related to TCA cycle intermediate transport |
| SLC25A1 | Mitochondrial citrate carrier | Context for mitochondrial metabolite transport |
| Complex II (succinate dehydrogenase) | Membrane-bound enzyme that oxidizes succinate | Central to succinate-dependent respiration assays |
| Mycobacterial oxidative phosphorylation enzymes | Targets for inhibitors of succinate-driven respiration | Drug discovery for tuberculosis |
| Conjugated oligoelectrolytes | Synthetic mimics of transmembrane electron transport | Bioelectrochemical and microbial electrosynthesis applications |
How Is succinate transmembrane transport Regulated?
Succinate transmembrane transport is regulated at multiple levels. The activity of sodium-coupled transporters such as SLC13A1 depends on the sodium gradient and on transcriptional control of the transporter gene. In mitochondria, succinate flux is coupled to the redox state of the respiratory chain and to the assembly and activity of complex II. Pharmacological inhibition, for example by valproate, can acutely reduce succinate transport in renal mitochondria. In epithelial systems, succinate chemosensing can regulate CFTR-dependent clearance, indicating that transport and signaling are integrated. Assays of oxidative phosphorylation provide a way to measure how inhibitors and genetic perturbations alter succinate-dependent respiration.
succinate transmembrane transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CFTR | Cystic fibrosis airway clearance | CFTR knockout or mutant airway epithelial cells |
| SDHA | Mitochondrial disease and cancer metabolism | SDHA knockout cell lines and complex II assembly assays |
| SDHB | Paraganglioma and pheochromocytoma predisposition | SDHB knockout or point-mutation models |
| SLC13A1 | Sulfate and succinate transport disorders | SLC13A1 knockout cells for transport assays |
| Mycobacterial oxidative phosphorylation enzymes | Tuberculosis drug target | Mycobacterial respiration inhibition assays |
Cystic fibrosis and airway clearance
Succinate chemosensing induces CFTR-dependent airway clearance, and this response is impaired in cystic fibrosis. This links succinate transport and sensing to epithelial physiology and suggests that modulating succinate handling could influence mucus clearance in disease.
Mitochondrial dysfunction and drug toxicity
Inhibition of succinate transport by valproate in renal mitochondria demonstrates that this process can be a site of drug-induced mitochondrial toxicity. Because complex II oxidizes succinate, defects in succinate handling can impair oxidative phosphorylation and contribute to mitochondrial disease phenotypes.
Cancer and metabolic reprogramming
Succinate dehydrogenase subunits are frequently altered in tumors, and succinate accumulation can affect signaling and epigenetics. Transport of succinate across membranes therefore influences the metabolic state of cancer cells and is relevant to oncometabolism.
Infectious disease and drug discovery
Mycobacterial oxidative phosphorylation, which depends on succinate-driven respiration, is a target for new anti-tuberculosis agents. Assays for inhibitors of this pathway are used to identify compounds that block succinate-dependent energy metabolism.
From succinate transmembrane transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC13A1 alter succinate uptake? | SLC13A1 knockout cell line |
| Does a point mutation in SDHA affect succinate oxidation? | SDHA point-mutation knock-in cells |
| Can a tagged transporter be used to follow succinate transport? | Tagged knock-in of SLC13A1 or SLC25A10 |
| Does overexpression of CFTR rescue succinate-induced clearance? | CFTR overexpression in cystic fibrosis airway cells |
| Can inhibitors block succinate-driven respiration? | Mycobacterial oxidative phosphorylation assay |
| Does complex II assembly require specific subunits? | Knockout of SDHB, SDHC, or SDHD |
How to Study the succinate transmembrane transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled succinate uptake | Rate and specificity of succinate transport | Characterizing SLC13 transporters |
| Oxygen consumption assay | Succinate-driven respiration and complex II activity | Inhibitor screening for oxidative phosphorylation |
| CRISPR knockout | Loss-of-function effects on succinate transport | Testing candidate transporter genes |
| CRISPR point mutation | Effect of specific residues on transport or catalysis | Structure-function studies of complex II |
| Tagged knock-in | Localization and interaction of transporters | Imaging and proteomics of succinate transporters |
| Overexpression | Gain-of-function effects on succinate handling | Rescue experiments in disease models |
| Epithelial electrophysiology | CFTR-dependent ion transport after succinate sensing | Cystic fibrosis research |
| Bioelectrochemical assays | Transmembrane electron transport mimics | Microbial electrosynthesis studies |
Transport assays with radiolabeled or fluorescent succinate
Direct measurement of succinate transmembrane transport can be performed using radiolabeled succinate or fluorescent analogs in cell and vesicle systems. These assays define kinetics, sodium dependence, and inhibitor sensitivity.
Respirometry and oxidative phosphorylation assays
Succinate-driven respiration can be measured using oxygen consumption assays to assess complex II activity and the effects of inhibitors. Such assays are used to screen for compounds that block mycobacterial or mitochondrial oxidative phosphorylation.
Genetic perturbation with CRISPR
CRISPR knockout, point mutation, and knock-in models allow causal testing of genes such as SLC13A1 and SDHA in succinate transport. These models can be combined with transport and respiration readouts to link genotype to function.
Epithelial physiology and imaging
Airway epithelial models can be used to study succinate chemosensing and CFTR-dependent clearance using imaging and electrophysiology. These methods connect succinate transport to tissue-level physiology.
How CRISPR Can Be Used to Study GO:0071422 succinate transmembrane transport
Knockout
CRISPR knockout of SLC13A1 or complex II subunits can abolish or reduce succinate transmembrane transport, allowing researchers to test causality. Knockout models are used with uptake and respiration assays to define the contribution of each gene.
Point Mutation
Point mutations in SDHA or transporter genes can be introduced to study specific residues required for succinate binding or catalysis. Such models help dissect structure-function relationships in succinate transport and oxidation.
Knock-in
Knock-in of tagged transporters, such as SLC13A1 with an epitope tag, enables localization and interaction studies without altering endogenous regulation. Knock-in of disease-associated variants can model human phenotypes.
Overexpression
Overexpression of CFTR or transporters can rescue or amplify succinate-dependent phenotypes in cell models. This approach is useful for gain-of-function studies and for validating drug targets.
How EDITGENE Supports succinate transmembrane transport Research
Researchers studying succinate transmembrane transport-related genes often need to determine whether a candidate gene is causally involved in succinate uptake, oxidation, or signaling. EDITGENE provides CRISPR-based cell models and screening services to test these hypotheses with publication-ready rigor.
Contact EDITGENE today to design your custom CRISPR model for succinate transmembrane transport research.
Frequently Asked Questions About succinate transmembrane transport
What is succinate transmembrane transport?
Succinate transmembrane transport (GO:0071422) is the process in which succinate is transported across a membrane, often by sodium-coupled transporters or as part of mitochondrial respiratory chain activity.
What genes are involved in succinate transmembrane transport?
Genes include SLC13A1 and related SLC13 family transporters, as well as SDHA, SDHB, SDHC, and SDHD of respiratory complex II.
Why is succinate transport important for mitochondria?
It delivers succinate to complex II for oxidation to fumarate, linking the TCA cycle to oxidative phosphorylation.
Can drugs inhibit succinate transport?
Yes, valproate inhibits succinate transport in rat renal mitochondria, and inhibitors of oxidative phosphorylation are actively sought in mycobacteria.
How is succinate transport studied experimentally?
Common methods include radiolabeled succinate uptake, oxygen consumption assays, and CRISPR-based genetic perturbation.
What diseases are linked to succinate transport?
Cystic fibrosis airway clearance, mitochondrial dysfunction, cancer metabolism, and tuberculosis drug discovery are linked to succinate transport.
What is the role of SLC13A1 in succinate transport?
SLC13A1 is a sodium-coupled transporter that recognizes Krebs cycle intermediates including succinate.
How does complex II handle succinate?
Complex II oxidizes succinate to fumarate at the inner mitochondrial membrane while transferring electrons to the quinone pool.
Can CRISPR be used to study succinate transport?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are used to test genes involved in succinate transport.
What is the GO ID for succinate transmembrane transport?
The GO ID is GO:0071422, under the biological_process ontology.
Conclusion
GO:0071422 succinate transmembrane transport is a fundamental biological process that connects succinate metabolism to mitochondrial energy production, cellular signaling, and disease. Its study relies on transport assays, respiration measurements, and CRISPR-based models of genes such as SLC13A1 and complex II subunits. Understanding this process offers opportunities for therapeutic intervention in cystic fibrosis, mitochondrial disorders, cancer, and infectious disease.
References
- 1. Markovich D. 2014. Na+-sulfate cotransporter SLC13A1.. Pflugers Arch 466(1):131-7 PMID: 24193406
- 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. Sousa JS et al.. 2018. Mitochondrial Respiratory Chain Complexes.. Subcell Biochem 87:167-227 PMID: 29464561
- 4. Quek G et al.. 2023. An n-Type Conjugated Oligoelectrolyte Mimics Transmembrane Electron Transport Proteins for Enhanced Microbial Electrosynthesis.. Angew Chem Int Ed Engl 62(33):e202305189 PMID: 37222113
- 5. Rumbach L et al.. 1989. Succinate transport inhibition by valproate in rat renal mitochondria.. Eur J Pharmacol 164(3):577-81 PMID: 2504612
- 6. Pajor AM. 1999. Sodium-coupled transporters for Krebs cycle intermediates.. Annu Rev Physiol 61:663-82 PMID: 10099705
- 7. Harden SA et al.. 2024. A simple assay for inhibitors of mycobacterial oxidative phosphorylation.. J Biol Chem 300(1):105483 PMID: 37992805
- 8. Lancaster CR. 2013. The di-heme family of respiratory complex II enzymes.. Biochim Biophys Acta 1827(5):679-87 PMID: 23466335
