GO:0015821 methionine transport: Amino Acid Transport Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015821 methionine transport is the directed movement of methionine (2-amino-4-(methylthio)butanoic acid) into, out of, or within a cell, or between cells, by means of a transporter or pore [QuickGO definition].
• Methionine transport systems are best characterized in bacteria such as Escherichia coli and Salmonella typhimurium, where high-affinity and low-affinity uptake systems have been genetically and biochemically defined.
• In the malaria parasite Plasmodium falciparum, methionine transport is essential for parasite survival and has been proposed as a drug target.
• In plants, source-to-sink transport of methionine is critical for seed protein quantity and quality in legumes.
• In mammals, placental methionine transport is altered in hyperhomocysteinemia, linking transport dysfunction to fetal growth and developmental outcomes.
• Methionine transport influences cancer biology, including ferroptosis sensitivity and response to immune checkpoint blockade.
Description
Methionine is an essential sulfur-containing amino acid that serves as a building block for protein synthesis and as a precursor for S-adenosylmethionine, the principal methyl donor in cellular methylation reactions. Because methionine cannot be synthesized de novo by many organisms, its uptake from the environment or from the bloodstream is a prerequisite for normal cellular function. GO:0015821 methionine transport describes the directed movement of methionine across biological membranes, a process mediated by specific transporter proteins and pores [QuickGO definition]. This term is a biological process and is synonymous with L-methionine transport.
methionine transport At A Glance
| GO ID | GO:0015821 |
|---|---|
| GO term | methionine transport |
| Ontology | biological_process |
| Synonym | L-methionine transport |
| Definition | The directed movement of methionine, 2-amino-4-(methylthio)butanoic acid, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| Major function | Mediates uptake, efflux, and distribution of methionine across cellular membranes |
| Related processes | Amino acid transport, sulfur amino acid metabolism, protein synthesis |
| Taxonomic scope | Bacteria, protozoa, plants, mammals |
What Is GO:0015821?
GO:0015821 methionine transport is defined as the directed movement of methionine, 2-amino-4-(methylthio)butanoic acid, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore [QuickGO definition]. This encompasses uptake from the extracellular environment, efflux, and intracellular compartmentalization of methionine. The process is distinct from methionine biosynthesis and from the transport of other amino acids, although some transporters exhibit overlapping substrate specificity.
Why Is methionine transport Important in Cell Biology?
Methionine transport is fundamental to cellular metabolism because methionine is required for protein synthesis and for the generation of S-adenosylmethionine, the universal methyl donor. Defects or alterations in methionine transport have been linked to diverse biological outcomes, including bacterial nutrient acquisition, parasite survival, plant seed protein quality, placental function in hyperhomocysteinemia, and cancer cell sensitivity to ferroptosis and immunotherapy. Understanding the molecular players and regulatory mechanisms of methionine transport is therefore relevant to microbiology, parasitology, plant science, and human disease research.
• Provides essential methionine for protein synthesis in organisms that cannot synthesize it de novo.
• Supports S-adenosylmethionine production and cellular methylation reactions.
• Influences bacterial growth and nutrient sensing in Escherichia coli and Salmonella typhimurium.
• Is essential for Plasmodium falciparum survival and represents a potential antimalarial target.
• Affects seed protein quantity and quality in legumes through source-to-sink transport.
• Is altered in placental tissue under hyperhomocysteinemic conditions, impacting fetal development.
• Modulates cancer cell sensitivity to ferroptosis and response to immune checkpoint blockade.
• Contributes to aminoaciduria phenotypes when renal tubular transport is impaired.
What Happens During methionine transport?
Substrate recognition and binding
In simple terms: The transporter first recognizes and grabs methionine from the surrounding environment.
Methionine transport begins with the recognition of methionine by a membrane-embedded transporter protein. In Escherichia coli, distinct transport systems for L-methionine have been characterized, including high-affinity and low-affinity systems that differ in their substrate specificity and regulation. In Salmonella typhimurium, methionine sulfoxide is transported by high-affinity methionine and glutamine transport systems, indicating that some transporters can recognize oxidized or related substrates. Substrate binding is typically stereospecific, with L-methionine being the preferred substrate.
Translocation across the membrane
In simple terms: The transporter then moves methionine across the cell membrane.
Following binding, the transporter undergoes conformational changes that translocate methionine across the lipid bilayer. In Pseudomonas aeruginosa, methionine transport activity has been demonstrated, confirming that this process occurs in diverse bacterial species. In the malaria parasite Plasmodium falciparum, methionine transport is essential for parasite growth and is mediated by specific transport activities that have been characterized biochemically. The direction of transport can be inward (uptake) or outward (efflux), depending on the transporter and cellular context [QuickGO definition].
Intracellular distribution and utilization
In simple terms: Once inside, methionine is distributed to where it is needed for protein synthesis and methylation.
After translocation, methionine is distributed within the cell to support protein synthesis and S-adenosylmethionine production. In plants, source-to-sink transport of methionine is critical for establishing seed protein quantity and quality in legumes, indicating that transport directs methionine to developing seeds. In mammals, placental transport of amino acids including methionine is essential for fetal development, and this process is altered in rats with methionine-induced hyperhomocysteinemia.
Regulation of transport activity
In simple terms: The cell can adjust how much methionine it takes up based on its needs.
Methionine transport activity is regulated in response to cellular demands and environmental conditions. In Escherichia coli, the expression and activity of methionine transport systems are subject to regulation, allowing adaptation to methionine availability. In cancer cells, intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade, indicating that methionine availability and transport influence therapeutic responses. These examples illustrate that methionine transport is not a constitutive process but is dynamically controlled.
Key Genes Involved in GO:0015821 methionine transport
The following genes and proteins have been experimentally implicated in methionine transport across bacteria, protozoa, plants, and mammals.
| Gene | Major Role | Research Relevance |
|---|---|---|
| metD (E. coli) | High-affinity L-methionine transport system | Model for bacterial methionine uptake and regulation |
| metP (E. coli) | Low-affinity L-methionine transport system | Secondary uptake system for methionine |
| metM (S. typhimurium) | High-affinity methionine transport | Also transports methionine sulfoxide |
| glnP (S. typhimurium) | Glutamine transport system | Contributes to methionine sulfoxide transport |
| PfMTR (P. falciparum) | Methionine transport in malaria parasite | Essential for parasite survival; drug target candidate |
| Methionine transporter (legume) | Source-to-sink methionine transport | Determines seed protein quantity and quality |
| Placental amino acid transporters | Methionine transport across placenta | Altered in hyperhomocysteinemia; impacts fetal growth |
| Renal tubular transporters | Methionine reabsorption | Dysfunction leads to aminoaciduria |
| SLC family transporters | Mammalian methionine transport | Broad substrate specificity; implicated in cancer |
| LAT1 (SLC7A5) | Large neutral amino acid transporter | Transports methionine in mammalian cells |
| SNAT2 (SLC38A2) | Sodium-coupled neutral amino acid transporter | Contributes to methionine uptake in mammalian cells |
| System A transporters | Methionine uptake in mammalian cells | Regulated by nutrient availability |
| System L transporters | Methionine efflux and exchange | Linked to mTOR signaling |
| Methionine permease (P. aeruginosa) | Methionine transport | Demonstrated in Pseudomonas aeruginosa |
| Bacterial ABC transporters | High-affinity methionine uptake | ATP-dependent transport systems |
| Plant amino acid permeases | Methionine loading into phloem | Source-to-sink transport in legumes |
| Parasite amino acid transporters | Methionine acquisition | Target for antimalarial development |
How Is methionine transport Regulated?
Methionine transport is regulated at multiple levels. In bacteria, the expression of methionine transport systems is controlled by methionine availability and by regulatory proteins that sense intracellular methionine levels. In Salmonella typhimurium, the high-affinity methionine transport system is subject to competition by methionine sulfoxide, indicating substrate-level regulation. In mammalian cells, methionine transport is influenced by nutrient signaling pathways, including mTOR, which coordinates amino acid availability with cell growth. In plants, source-to-sink transport of methionine is developmentally regulated to meet the demands of seed filling. In the placenta, methionine transport is altered under hyperhomocysteinemic conditions, suggesting regulation by homocysteine or related metabolites.
methionine transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC7A5 (LAT1) | Cancer metabolism and ferroptosis | Knockout cancer cell lines treated with methionine deprivation |
| Placental transporters | Hyperhomocysteinemia and fetal growth | Rat model of methionine-induced hyperhomocysteinemia |
| Renal tubular transporters | Aminoaciduria | Knockout mouse models of renal amino acid transport |
| PfMTR | Malaria parasite survival | Plasmodium falciparum culture with transport inhibitors |
| Legume amino acid permeases | Seed protein quality | Knockout or overexpression in legume plants |
Cancer and ferroptosis
Methionine transport influences cancer cell metabolism and therapeutic response. Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade, demonstrating that methionine availability and transport are critical determinants of ferroptosis sensitivity and immunotherapy efficacy. These findings suggest that targeting methionine transport could be a strategy to enhance cancer treatment.
Hyperhomocysteinemia and placental dysfunction
In rats with methionine-induced hyperhomocysteinemia, placental transport of amino acids including methionine is altered, which may contribute to fetal growth restriction and developmental abnormalities. This links methionine transport dysfunction to pregnancy complications and fetal programming.
Aminoaciduria and renal transport defects
Aminoaciduria, the excessive excretion of amino acids in urine, can result from defective renal tubular transport of amino acids including methionine. This condition illustrates the importance of methionine transport in kidney function and systemic amino acid homeostasis.
Infectious disease and parasite metabolism
Methionine transport is essential for the survival of the malaria parasite Plasmodium falciparum, making it a potential target for antimalarial drug development. Similarly, bacterial methionine transport systems are required for growth and virulence, as demonstrated in Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa.
From methionine transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does knockout of a candidate methionine transporter reduce methionine uptake? | CRISPR knockout cell line or bacterial strain |
| Does a point mutation in the transporter alter substrate specificity? | CRISPR point mutation knock-in cell line |
| Does overexpression of a transporter increase methionine uptake and downstream metabolism? | CRISPR overexpression cell line |
| Does tagging a transporter with a fluorescent protein affect its localization? | CRISPR tagged knock-in cell line |
| Does knockout of a placental transporter affect fetal growth? | CRISPR knockout mouse model |
| Does knockout of a plant transporter alter seed protein content? | CRISPR knockout legume plant |
How to Study the methionine transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled methionine uptake | Transport activity | Characterizing bacterial and parasite transporters |
| CRISPR knockout screen | Genes required for methionine transport | Identifying novel transporters in mammalian cells |
| RNA-seq | Expression of transporter genes | Comparing methionine-replete vs. deprived conditions |
| Proteomics | Protein abundance of transporters | Quantifying transport machinery |
| Fluorescence microscopy | Subcellular localization | Determining membrane targeting of transporters |
| Seed protein analysis | Protein quantity and quality | Assessing source-to-sink transport in legumes |
| Placental perfusion | Amino acid transport across placenta | Studying hyperhomocysteinemia effects |
| Amino acid excretion assay | Urinary amino acid levels | Diagnosing aminoaciduria |
Transport assays
Radiolabeled or fluorescent methionine uptake assays are used to measure transport activity in cells or membrane vesicles. These assays have been used to characterize methionine transport systems in Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Plasmodium falciparum.
Genetic screens and knockout studies
CRISPR knockout screens and classical genetic approaches identify genes required for methionine transport. In bacteria, mutants defective in methionine transport have been isolated and characterized. In mammalian cells, CRISPR knockout of candidate transporters can reveal their contribution to methionine uptake and metabolism.
Transcriptomics and proteomics
RNA-seq and proteomics can quantify the expression of methionine transporters under different conditions, such as methionine deprivation or hyperhomocysteinemia. These methods help identify regulatory mechanisms and compensatory changes in transport systems.
Imaging and localization studies
Fluorescence microscopy of tagged transporters can determine their subcellular localization and trafficking. This approach is applicable to bacterial, parasite, plant, and mammalian systems.
How CRISPR Can Be Used to Study GO:0015821 methionine transport
Knockout
CRISPR knockout of candidate methionine transporter genes can abolish or reduce methionine uptake, allowing researchers to determine which transporters are essential for the process. For example, knockout of SLC7A5 or other transporters in cancer cell lines can reveal their role in methionine dependence and ferroptosis sensitivity. In bacteria, targeted knockout of metD or metP can confirm their function in methionine transport.
Point Mutation
CRISPR point mutation can introduce specific amino acid substitutions in transporter genes to test structure-function relationships. For instance, mutating residues in the substrate-binding pocket of a methionine transporter can alter its affinity or specificity, as suggested by studies on methionine sulfoxide transport in Salmonella typhimurium.
Knock-in
CRISPR knock-in can be used to tag endogenous transporters with fluorescent or affinity tags, enabling visualization and purification. This approach has been applied to study the localization of amino acid transporters in Plasmodium falciparum and plants.
Overexpression
CRISPR-mediated overexpression of a methionine transporter can increase uptake capacity and amplify downstream metabolic effects. Overexpression of transporters in cancer cells can enhance methionine uptake and alter sensitivity to methionine deprivation. In plants, overexpression of amino acid permeases can increase seed methionine content.
How EDITGENE Supports methionine transport Research
Researchers studying methionine transport-related genes often need to determine whether a candidate gene is causally involved in methionine uptake, distribution, or disease. EDITGENE provides a comprehensive suite of CRISPR-based services to enable these investigations, from knockout to knock-in and library screening.
Contact EDITGENE today to design your custom CRISPR model for methionine transport research.
Frequently Asked Questions About methionine transport
What is methionine transport?
Methionine transport (GO:0015821) is the directed movement of methionine into, out of, or within a cell, or between cells, by means of a transporter or pore [QuickGO definition].
What genes are involved in methionine transport?
Genes involved include metD and metP in Escherichia coli, metM and glnP in Salmonella typhimurium, PfMTR in Plasmodium falciparum, and SLC7A5 (LAT1) in mammals.
How is methionine transported across cell membranes?
Methionine is transported by specific membrane proteins that recognize and translocate the amino acid across the lipid bilayer, as demonstrated in bacteria, parasites, and mammals.
Why is methionine transport important in cancer?
Methionine transport influences cancer cell sensitivity to ferroptosis and response to immune checkpoint blockade, making it a potential therapeutic target.
Is methionine transport altered in hyperhomocysteinemia?
Yes, placental transport of amino acids including methionine is altered in rats with methionine-induced hyperhomocysteinemia.
What is the role of methionine transport in plants?
Source-to-sink transport of methionine is critical for establishing seed protein quantity and quality in legumes.
Can methionine transport be targeted for malaria treatment?
Methionine transport is essential for Plasmodium falciparum survival, and its transporters are considered potential antimalarial drug targets.
What diseases are associated with defective methionine transport?
Defective renal tubular transport can cause aminoaciduria, and altered placental transport is linked to fetal growth issues in hyperhomocysteinemia.
How can CRISPR be used to study methionine transport?
CRISPR knockout, point mutation, knock-in, and overexpression models allow researchers to test the function of specific transporters in methionine uptake and disease.
What methods measure methionine transport activity?
Radiolabeled uptake assays, genetic screens, transcriptomics, proteomics, and imaging are commonly used to measure and study methionine transport.
Conclusion
GO:0015821 methionine transport is a fundamental biological process that ensures the availability of methionine for protein synthesis and methylation. Its molecular players have been characterized across bacteria, parasites, plants, and mammals, and its dysfunction is linked to cancer, hyperhomocysteinemia, aminoaciduria, and infectious disease. Continued research using CRISPR-based models and advanced omics will further elucidate the regulatory networks and therapeutic potential of methionine transport.
References
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- 2. Montie TC et al.. 1979. Methionine transport in Pseudomonas aeruginosa.. Can J Microbiol 25(9):1103-7 PMID: 120222
- 3. Milyutina YP et al.. 2024. Placental Transport of Amino Acids in Rats with Methionine-Induced Hyperhomocysteinemia.. Biochemistry (Mosc) 89(10):1711-1726 PMID: 39523111
- 4. Kadner RJ. 1974. Transport systems for L-methionine in Escherichia coli.. J Bacteriol 117(1):232-41 PMID: 4587605
- 5. Ayling PD. 1981. Methionine sulfoxide is transported by high-affinity methionine and glutamine transport systems in Salmonella typhimurium.. J Bacteriol 148(2):514-20 PMID: 7028716
- 6. Cobbold SA et al.. 2011. Methionine transport in the malaria parasite Plasmodium falciparum.. Int J Parasitol 41(1):125-35 PMID: 20851123
- 7. Garneau MG et al.. 2021. Role of source-to-sink transport of methionine in establishing seed protein quantity and quality in legumes.. Plant Physiol 187(4):2134-2155 PMID: 34618032
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