GO:0043090 amino acid import: Nutrient Uptake Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0043090 (amino acid import) is the directed movement of amino acids into a cell or organelle, also known as amino acid uptake.
• Amino acid import is mediated by plasma-membrane and organellar transporters and is tightly coupled to nutrient sensing, redox balance and cell growth.
• In yeast, amino acid import is regulated by the TOR pathway and is inhibited by the immunosuppressant FK506, linking transport to growth signaling.
• The integrated stress response (ISR) reprograms amino acid metabolism and import to resist oxidative stress and maintain homeostasis.
• SLC7A5 (LAT1) is required for cancer cell growth under arginine-limited conditions, showing that import supports tumor adaptation.
• Mitochondrial and peroxisomal import routes, such as SLC25A45-mediated methylated amino acid import and peroxisomal protein import, expand the subcellular scope of amino acid and metabolite import.
Description
Amino acid import (GO:0043090) is the directed movement of amino acids into a cell or organelle, a process also referred to as amino acid uptake. This biological process supplies the building blocks for protein synthesis, fuels central carbon metabolism, and feeds signaling pathways that sense nutrient availability. Because amino acids cannot freely diffuse across lipid bilayers at rates sufficient for growth, dedicated transport systems are required at the plasma membrane and at organellar membranes.
amino acid import At A Glance
| GO ID | GO:0043090 |
|---|---|
| GO term | amino acid import |
| Ontology | biological_process |
| Synonym | amino acid uptake |
| Definition | The directed movement of amino acids into a cell or organelle. |
| Major function | Supplies amino acids for protein synthesis, metabolism and signaling. |
| Subcellular locations | Plasma membrane, mitochondria, peroxisomes and other organelles. |
| Representative transporters | SLC7A5, SLC25A45 and yeast amino acid permeases. |
| Regulatory inputs | TOR signaling, integrated stress response and redox status. |
What Is GO:0043090?
In this article, amino acid import is defined as the directed movement of amino acids into a cell or organelle, consistent with the QuickGO definition for GO:0043090. The term covers uptake across the plasma membrane as well as transport into organelles such as mitochondria and peroxisomes, and it is synonymous with amino acid uptake.
Why Is amino acid import Important in Cell Biology?
Amino acid import is important because it determines the intracellular availability of amino acids for protein synthesis, redox homeostasis and epigenetic regulation, and its dysregulation contributes to cancer, metabolic stress and organellar dysfunction.
• Provides amino acids for protein synthesis and cell growth.
• Supports cancer cell proliferation under nutrient-limited conditions.
• Links nutrient status to the integrated stress response and oxidative stress resistance.
• Connects amino acid metabolism to redox balance and epigenetic regulation.
• Is regulated by TOR signaling and is sensitive to FK506 in yeast.
• Includes mitochondrial import of methylated amino acids for carnitine synthesis.
• Includes peroxisomal import pathways that protect against pexophagy and ROS.
• Is a target for understanding nutrient sensing and metabolic disease.
What Happens During amino acid import?
Substrate recognition at the membrane
In simple terms: Transporters first recognize and bind the amino acid they will carry.
Amino acid import begins when membrane transporters recognize their substrates with sufficient specificity to discriminate among chemically similar amino acids. In Saccharomyces cerevisiae, multiple permeases with overlapping specificities mediate uptake, and their regulation determines which amino acids enter the cell. The immunosuppressant FK506 inhibits amino acid import in yeast, indicating that substrate recognition and transport are coupled to cellular signaling.
Translocation across the lipid bilayer
In simple terms: The bound amino acid is moved across the membrane into the cell.
After recognition, the transporter undergoes conformational changes that translocate the amino acid across the lipid bilayer into the cytoplasm. This step is energy-dependent and is integrated with the cell's metabolic state, because amino acid import must match biosynthetic demand. In mammalian cells, SLC7A5-mediated transport supports growth when extracellular arginine is limited, demonstrating that translocation capacity can be rate-limiting for proliferation.
Mitochondrial amino acid import
In simple terms: Some amino acids are moved into mitochondria for specialized reactions.
Mitochondria import specific amino acids and amino acid derivatives for organellar metabolism. Machine-learning-guided discovery identified SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis, linking mitochondrial transport to carnitine production. This illustrates that amino acid import is not restricted to the plasma membrane but also occurs at organellar membranes.
Peroxisomal import and organelle homeostasis
In simple terms: Peroxisomes import proteins and metabolites through specialized machinery.
Peroxisomal import occurs through a nuclear pore-like phase, and PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS. These findings show that import into organelles is mechanistically related to nuclear pore transport and is coupled to organelle quality control. Amino acid import into peroxisomes therefore contributes to peroxisomal metabolism and stress resistance.
Coupling to stress and nutrient signaling
In simple terms: Import is adjusted when cells face stress or changing nutrients.
The integrated stress response regulates amino acid metabolism and resistance to oxidative stress, coordinating import with cellular defense. In yeast, TOR signaling and FK506-sensitive pathways control amino acid import, linking transport to growth control. Amino acid metabolism, redox balance and epigenetic regulation are interconnected, so import activity influences gene expression and antioxidant capacity.
Key Genes Involved in GO:0043090 amino acid import
The following genes and proteins are representative mediators or regulators of amino acid import across cellular and organellar membranes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC7A5 | Plasma-membrane amino acid transporter | Required for cancer cell growth under arginine-limited conditions |
| SLC25A45 | Mitochondrial methylated amino acid import | Mediates carnitine synthesis |
| PEX13 | Peroxisomal import machinery | Prevents pexophagy by regulating ubiquitinated PEX5 and ROS |
| PEX5 | Peroxisomal import receptor | Ubiquitination and import regulation |
| GCN2 | Integrated stress response kinase | Links amino acid status to stress response |
| TOR | Nutrient signaling kinase | Regulates amino acid import and growth |
| Yeast amino acid permeases | Plasma-membrane uptake | Model for transport regulation |
| SLC family transporters | Amino acid transport | Broad family mediating import |
| ATF4 | ISR transcription factor | Regulates amino acid metabolism genes |
| FKBP12 | FK506-binding protein | Mediates FK506 inhibition of import |
| PEX14 | Peroxisomal docking protein | Import complex component |
| PEX17 | Peroxisomal import factor | Import complex component |
| SLC3A2 | Transporter accessory subunit | Partners with SLC7A5 |
| SLC1A5 | Glutamine transporter | Supports amino acid import networks |
| SLC38A2 | Sodium-coupled amino acid transporter | Mediates amino acid uptake |
| SLC43A1 | Amino acid transporter | Mediates amino acid uptake |
| SLC16A10 | Aromatic amino acid transporter | Mediates amino acid uptake |
How Is amino acid import Regulated?
Amino acid import is regulated by nutrient-sensing and stress-responsive pathways. In yeast, the immunosuppressant FK506 inhibits amino acid import, implicating calcineurin- and TOR-linked signaling in transport control. The integrated stress response regulates amino acid metabolism and resistance to oxidative stress, adjusting import to cellular needs. Amino acid metabolism, redox balance and epigenetic regulation are interconnected, so import is tuned to both metabolic and transcriptional states.
amino acid import and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC7A5 | Cancer growth under arginine limitation | Knockout in cancer cell lines |
| SLC25A45 | Mitochondrial metabolism and carnitine synthesis | Knockout in metabolic cell models |
| PEX13 | Peroxisomal dysfunction and pexophagy | Knockout in peroxisomal disease models |
| PEX5 | Peroxisomal import defects | Point mutation in import receptor |
| GCN2 | Integrated stress response and oxidative stress | Knockout in stress models |
Cancer metabolism and nutrient limitation
SLC7A5 is required for cancer cell growth under arginine-limited conditions, showing that amino acid import supports tumor adaptation to nutrient stress. Amino acid metabolism, redox balance and epigenetic regulation are interconnected in cancer, so import activity influences proliferation and stress resistance.
Oxidative stress and integrated stress response
The integrated stress response regulates amino acid metabolism and resistance to oxidative stress, linking import to cellular defense. Dysregulation of this response can impair the ability of cells to maintain amino acid homeostasis under stress.
Organellar dysfunction
Peroxisomal import defects and dysregulated pexophagy are associated with organelle dysfunction, as PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS. Peroxisomal import occurs through a nuclear pore-like phase, and disruption of this process affects organelle function.
Mitochondrial metabolism and carnitine synthesis
SLC25A45 mediates mitochondrial methylated amino acid import and carnitine synthesis, connecting mitochondrial import to metabolic pathways. Defects in mitochondrial amino acid import may therefore affect carnitine-dependent metabolism.
From amino acid import-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is SLC7A5 required for growth under arginine limitation? | Knockout cell line |
| Does SLC25A45 mediate mitochondrial amino acid import? | Knockout and overexpression models |
| How does PEX13 regulate pexophagy? | Knockout and point-mutation models |
| What is the role of PEX5 ubiquitination in import? | Point-mutation knock-in |
| How does the ISR regulate amino acid import? | Knockout of GCN2 or ATF4 |
| Does FK506-sensitive signaling control import? | Yeast knockout and drug-treatment models |
How to Study the amino acid import Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled uptake assay | Amino acid import rate | Transporter characterization |
| CRISPR knockout screen | Genes required for import | Cancer nutrient limitation |
| Metabolomics | Intracellular amino acid levels | Mitochondrial import studies |
| Proteomics | Transporter abundance | Organellar import analysis |
| Stress reporter assay | ISR activation | Oxidative stress studies |
| Drug sensitivity assay | FK506 inhibition of import | Yeast signaling studies |
| Imaging | Organelle import dynamics | Peroxisomal import |
| Epigenetic profiling | Chromatin changes | Amino acid metabolism studies |
Transport assays
Radiolabeled or fluorescent amino acid uptake assays measure import activity directly in cells and organelles. These assays are used to define substrate specificity and regulation of transporters.
Genetic screens and knockout libraries
Knockout and CRISPR library screens identify genes required for amino acid import and growth under nutrient-limited conditions. Such screens can reveal transporter dependencies in cancer cells.
Metabolic and proteomic profiling
Metabolomics and proteomics quantify intracellular amino acid pools and transporter abundance, linking import to metabolism. These approaches are used to study mitochondrial and peroxisomal import.
Stress and signaling assays
Reporter assays and stress-response markers measure how the integrated stress response and TOR signaling regulate import. These methods are applied in yeast and mammalian models.
How CRISPR Can Be Used to Study GO:0043090 amino acid import
Knockout
CRISPR knockout of transporters such as SLC7A5 can test whether amino acid import is required for growth under nutrient-limited conditions. Knockout of PEX13 or PEX5 can reveal roles in peroxisomal import and pexophagy.
Point Mutation
Point mutations in import receptors such as PEX5 can dissect ubiquitination-dependent steps in peroxisomal import. Point mutations in transporter genes can define substrate-binding residues.
Knock-in
Knock-in of tagged transporters allows visualization and affinity purification of import complexes. Tagged knock-in of SLC25A45 can localize mitochondrial import activity.
Overexpression
Overexpression of amino acid transporters can increase import capacity and test sufficiency in growth and stress models. Overexpression of SLC7A5 can support growth under arginine limitation.
How EDITGENE Supports amino acid import Research
Researchers studying amino acid import-related genes often need to determine whether a candidate gene is causally involved in transport, growth or stress resistance, and CRISPR-based models provide a direct way to test these hypotheses.
Contact EDITGENE today to design your custom CRISPR model for amino acid import research.
Frequently Asked Questions About amino acid import
What is amino acid import (GO:0043090)?
Amino acid import is the directed movement of amino acids into a cell or organelle, also called amino acid uptake.
What genes are involved in amino acid import?
Genes include SLC7A5, SLC25A45, PEX13, PEX5 and yeast amino acid permeases.
How is amino acid import regulated?
It is regulated by TOR signaling, the integrated stress response and redox status.
Why is amino acid import important in cancer?
SLC7A5 is required for cancer cell growth under arginine-limited conditions.
Does amino acid import occur in mitochondria?
Yes, SLC25A45 mediates mitochondrial methylated amino acid import and carnitine synthesis.
What is the role of peroxisomes in import?
Peroxisomal import occurs through a nuclear pore-like phase, and PEX13 regulates pexophagy and ROS.
How can I study amino acid import in the lab?
Use uptake assays, CRISPR screens, metabolomics and proteomics.
What is the integrated stress response?
It is a pathway that regulates amino acid metabolism and resistance to oxidative stress.
Does FK506 affect amino acid import?
Yes, FK506 inhibits amino acid import in Saccharomyces cerevisiae.
What CRISPR models are used for import studies?
Knockout, point-mutation, knock-in and overexpression models are used.
Conclusion
Amino acid import (GO:0043090) is a central biological process that supplies cells and organelles with amino acids for growth, metabolism and stress defense. Its regulation by TOR signaling, the integrated stress response and redox pathways makes it a key node in cancer and metabolic research. CRISPR-based models and omics methods provide powerful tools to dissect the genes and mechanisms underlying amino acid import.
References
- 1. Khan A et al.. 2025. Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis.. Cell Metab 37(11):2220-2232.e8 PMID: 41075780
- 2. Harding HP et al.. 2003. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress.. Mol Cell 11(3):619-33 PMID: 12667446
- 3. Demers ND et al.. 2023. PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS.. Autophagy 19(6):1781-1802 PMID: 36541703
- 4. Gao Y et al.. 2022. Protein import into peroxisomes occurs through a nuclear pore-like phase.. Science 378(6625):eadf3971 PMID: 36520918
- 5. Dunlap KN et al.. 2025. SLC7A5 is required for cancer cell growth under arginine-limited conditions.. Cell Rep 44(1):115130 PMID: 39756034
- 6. Bianchi F et al.. 2019. Regulation of Amino Acid Transport in Saccharomyces cerevisiae.. Microbiol Mol Biol Rev 83(4) PMID: 31619504
- 7. Heitman J et al.. 1993. The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae.. Mol Cell Biol 13(8):5010-9 PMID: 7687745
- 8. Li X et al.. 2024. Amino acid metabolism, redox balance and epigenetic regulation in cancer.. FEBS J 291(3):412-429 PMID: 37129434
