GO:0140354 lipid import into cell: Transport Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0140354 (lipid import into cell) is the directed movement of a lipid from outside a cell into the cell, occurring either by transport across the plasma membrane or by endocytosis.
• Lipid import supplies cells with fatty acids, cholesterol, phospholipids and other lipid species that are essential for membrane biogenesis, energy production and signalling.
• Mitochondria are a major destination for imported lipids; phospholipid and fatty acid trafficking between the plasma membrane, lipid droplets and mitochondria is tightly coordinated.
• Mitochondrial fatty acid synthesis is now recognized as a central regulator of mammalian oxidative metabolism, linking lipid import and synthesis to cellular energy status.
• Proteins such as Transgelin 2, SCARB1 and Seipin control lipid uptake, trafficking and storage, and their dysfunction has been linked to cancer, metabolic disease and immune dysfunction.
• CRISPR knockout, point-mutation, knock-in and overexpression models are powerful tools for dissecting the causal roles of lipid-import genes in health and disease.
Description
Lipid import into cell (GO:0140354) describes the directed movement of a lipid molecule from the extracellular space into the interior of a cell. This process is fundamental because lipids are not only structural building blocks of membranes but also signalling molecules and substrates for energy production. Cells can acquire lipids either by de novo synthesis or by uptake from the environment, and the balance between these routes determines membrane composition, energy storage and cellular signalling. The QuickGO definition specifies that lipid import may occur via transport across the plasma membrane or via endocytosis, highlighting the mechanistic diversity of this process. Research on lipid import has accelerated because dysregulated lipid uptake is a hallmark of many diseases, including cancer, metabolic disorders and immune dysfunction. For example, Transgelin 2 has been shown to guard T cell lipid metabolism and antitumour function, directly linking lipid handling to immune surveillance. In clear cell renal cell carcinoma, CircABCA1 promotes tumour progression by reprogramming cholesterol metabolism and facilitating M2 macrophage polarization through stabilization of SCARB1 mRNA. These findings illustrate that lipid import is not a passive process but a regulated, disease-relevant pathway. For researchers, GO:0140354 provides a controlled vocabulary to annotate genes and proteins involved in lipid uptake, making it easier to compare datasets, interpret omics results and design mechanistic experiments. Understanding the molecular players, regulatory inputs and disease connections of lipid import is therefore essential for both basic cell biology and translational research.
lipid import into cell At A Glance
| GO ID | GO:0140354 |
|---|---|
| GO term | lipid import into cell |
| Ontology | biological_process |
| Synonym | lipid uptake |
| Definition | The directed movement of a lipid from outside of a cell into a cell. This may occur via transport across the plasma membrane or via endocytosis. |
| Major function | Acquisition of extracellular lipids for membrane biogenesis, energy production, lipid storage and signalling |
| Related processes | Phospholipid synthesis and transport, fatty acid trafficking between lipid droplets and mitochondria, mitochondrial fatty acid synthesis |
| Cellular locations | Plasma membrane, endocytic vesicles, endoplasmic reticulum, mitochondria, lipid droplets |
| Representative regulators | Transgelin 2, SCARB1, Seipin, CircABCA1 |
What Is GO:0140354?
In simple terms, lipid import into cell is the process by which a cell takes up lipid molecules from its surroundings. According to the QuickGO definition, it is the directed movement of a lipid from outside of a cell into a cell, and this may occur either via transport across the plasma membrane or via endocytosis. The term is a biological process and is also known by the synonym lipid uptake. It encompasses the movement of fatty acids, cholesterol, phospholipids and other lipid species into the cell, and it is distinct from intracellular lipid trafficking or lipid synthesis, although these processes are functionally interconnected.
Why Is lipid import into cell Important in Cell Biology?
Lipid import into cell is important because it determines the cellular lipid supply that supports membrane assembly, energy homeostasis and signal transduction, and its dysregulation contributes to cancer, metabolic disease and immune dysfunction. Because lipids cannot freely diffuse across membranes in a controlled manner, cells rely on dedicated transport and endocytic machinery to import specific lipid species, and the activity of this machinery directly influences cell fate and function. Understanding GO:0140354 therefore helps researchers connect extracellular lipid availability to intracellular processes such as mitochondrial metabolism, lipid droplet dynamics and immune cell activation.
• Provides essential fatty acids and cholesterol for membrane biogenesis and cell growth.
• Supplies substrates for mitochondrial fatty acid oxidation and energy production.
• Controls lipid storage in lipid droplets and prevents lipotoxicity.
• Regulates immune cell function, including T cell antitumour activity.
• Is reprogrammed in cancer, exemplified by cholesterol metabolism in clear cell renal cell carcinoma.
• Links endoplasmic reticulum-mitochondria contact sites to calcium and metabolic control in adipocytes.
• Influences mitochondrial permeability and fatty acid oxidation under stress.
• Provides a functional annotation framework for omics and CRISPR screening data.
• Represents a druggable axis for metabolic and oncological diseases.
• Connects extracellular nutrient status to intracellular signalling and gene expression.
What Happens During lipid import into cell?
Recognition and binding of extracellular lipids
In simple terms: The cell first recognizes and binds lipid molecules or lipid-carrying particles at its surface.
Lipid import begins when lipids or lipid-associated particles in the extracellular space interact with the cell surface. This can involve membrane receptors and lipid-binding proteins that capture fatty acids, cholesterol or phospholipids and present them to transport or endocytic machinery. The specificity of these interactions determines which lipid species are preferentially imported, and it is a key point of regulation for cellular lipid composition.
Transport across the plasma membrane
In simple terms: Some lipids are moved directly across the outer membrane of the cell.
One route of lipid import is direct transport across the plasma membrane. This may involve membrane proteins that facilitate the movement of lipid molecules from the outer leaflet to the inner leaflet or into the cytosol. Because lipids are hydrophobic, their transfer across the aqueous environment of the membrane requires specialized handling, and the imported lipids are often rapidly bound by intracellular carriers to prevent aggregation and toxicity.
Endocytic uptake of lipids
In simple terms: Alternatively, the cell can engulf lipids or lipid-carrying particles in membrane-bound vesicles.
The second major route is endocytosis, in which lipids or lipid-protein complexes are internalized within vesicles derived from the plasma membrane. This pathway allows the cell to import large amounts of lipid and to deliver specific lipid species to intracellular compartments. Endocytic uptake is particularly important for cholesterol-rich particles and for lipids that are associated with carrier proteins.
Intracellular trafficking to organelles
In simple terms: Once inside, lipids are delivered to the organelles that need them.
After import, lipids are distributed to intracellular destinations such as the endoplasmic reticulum, mitochondria and lipid droplets. Phospholipid synthesis and transport in mammalian cells depend on coordinated trafficking between these compartments. Fatty acid trafficking between lipid droplets and mitochondria is an emerging area of research, and it determines whether imported fatty acids are stored or oxidized. Mitochondria themselves contain distinct lipid populations, and their lipid composition is maintained by import and local synthesis.
Integration with mitochondrial metabolism
In simple terms: Imported lipids can be burned for energy or used to build mitochondrial membranes.
Imported fatty acids can enter mitochondria for beta-oxidation, while imported phospholipids contribute to mitochondrial membrane architecture. Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism, indicating that lipid import and local lipid synthesis are functionally coupled. Stress conditions can modulate mitochondrial permeability and thereby influence fatty acid oxidation, further linking lipid import to cellular stress responses.
Key Genes Involved in GO:0140354 lipid import into cell
The following genes and proteins have been experimentally implicated in lipid import into cell or in the downstream trafficking and metabolism of imported lipids.
| Gene | Major Role | Research Relevance |
|---|---|---|
| TAGLN2 | Guards T cell lipid metabolism and antitumour function | Links lipid handling to immune surveillance and cancer immunotherapy |
| SCARB1 | Cholesterol uptake receptor; stabilized by IGF2BP3 in ccRCC | Promotes M2 macrophage polarization and tumour progression |
| ABCA1 | Cholesterol efflux and lipid transport; CircABCA1 regulates its pathway | Reprogrammes cholesterol metabolism in clear cell renal cell carcinoma |
| IGF2BP3 | RNA-binding protein that stabilizes SCARB1 mRNA | Connects RNA stability to cholesterol import in cancer |
| BSCL2 (Seipin) | Localizes at ER-mitochondria contact sites; controls calcium import and metabolism | Regulates adipocyte metabolism and lipid trafficking |
| Mitochondrial fatty acid synthesis enzymes | Generate lipoic acid and other mitochondrial lipids | Central regulators of oxidative metabolism |
| Lipid droplet-associated proteins | Store and release fatty acids | Mediate fatty acid trafficking between lipid droplets and mitochondria |
| Mitochondrial phospholipid transporters | Maintain mitochondrial lipid composition | Essential for mitochondrial membrane integrity |
| Endocytic machinery components | Mediate vesicular uptake of lipids | Enable endocytic route of lipid import |
| Plasma membrane lipid transporters | Facilitate lipid movement across the plasma membrane | Control direct lipid uptake |
| Stress granule proteins | Modulate mitochondrial permeability and fatty acid oxidation | Link stress responses to lipid metabolism |
| Phospholipid synthesis enzymes | Convert imported lipids into membrane phospholipids | Determine membrane lipid composition |
| Fatty acid binding proteins | Carry imported fatty acids within the cell | Prevent lipotoxicity and direct fatty acids to organelles |
| ER-mitochondria contact site proteins | Coordinate lipid and calcium exchange | Regulate metabolic homeostasis in adipocytes |
| Transgelin family proteins | Regulate actin and lipid metabolism | Potential targets for immune-metabolism studies |
How Is lipid import into cell Regulated?
Lipid import into cell is regulated at multiple levels. Extracellular lipid availability and the expression of transport and endocytic machinery determine the rate of uptake. Intracellular demand for lipids, including membrane biogenesis and energy production, feeds back on import pathways. Mitochondrial fatty acid synthesis acts as a central regulator of oxidative metabolism, coupling lipid import to mitochondrial function. Stress conditions can modulate mitochondrial permeability and fatty acid oxidation, providing an additional layer of regulation. In immune cells, Transgelin 2 guards lipid metabolism and antitumour function, indicating that cell-type-specific regulators control lipid import and utilization. In cancer, RNA-binding proteins such as IGF2BP3 can stabilize transcripts encoding lipid uptake receptors, thereby increasing lipid import. Seipin at ER-mitochondria contact sites controls calcium import and metabolism in adipocytes, linking contact site biology to lipid handling.
lipid import into cell and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SCARB1 | Clear cell renal cell carcinoma; cholesterol uptake and M2 macrophage polarization | Knockout and overexpression in ccRCC cell lines; macrophage co-culture |
| TAGLN2 | T cell lipid metabolism and antitumour immunity | Knockout T cells in syngeneic tumour models |
| BSCL2 (Seipin) | Adipocyte metabolism and ER-mitochondria contact site function | Knockout adipocytes; calcium and lipid flux assays |
| IGF2BP3 | mRNA stabilization of SCARB1 in cancer | Knockdown and RNA immunoprecipitation in ccRCC cells |
| Mitochondrial fatty acid synthesis enzymes | Oxidative metabolism and metabolic disease | Knockout and point-mutation models in cultured cells |
Cancer and tumour metabolism
Reprogrammed lipid metabolism is a hallmark of cancer, and lipid import supports the membrane and energy demands of proliferating tumour cells. In clear cell renal cell carcinoma, CircABCA1 promotes tumour progression by reprogramming cholesterol metabolism and facilitating M2 macrophage polarization through IGF2BP3-mediated stabilization of SCARB1 mRNA. This demonstrates that lipid import receptors such as SCARB1 can be co-opted to support an immunosuppressive tumour microenvironment. Transgelin 2 guards T cell lipid metabolism and antitumour function, indicating that lipid handling in immune cells also influences tumour control.
Metabolic and adipose tissue disorders
Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes, linking lipid import and contact site function to adipose tissue biology. Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism, and its dysregulation may contribute to metabolic disease. Fatty acid trafficking between lipid droplets and mitochondria is an emerging perspective that is relevant to obesity, insulin resistance and lipotoxicity.
Mitochondrial dysfunction and stress responses
Mitochondria depend on imported lipids for membrane integrity and function, and altered lipid import can affect oxidative metabolism. Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability, showing that cellular stress pathways intersect with lipid utilization. These connections suggest that defects in lipid import or trafficking may contribute to mitochondrial dysfunction in a range of pathologies.
From lipid import into cell-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for lipid import? | CRISPR knockout cell line followed by lipid uptake assays |
| Does a specific residue control transport activity? | Point-mutation knock-in of the endogenous locus |
| How does a disease-associated variant affect lipid import? | Knock-in of the variant and functional lipid flux measurement |
| Where does the protein localize during lipid import? | Tagged knock-in with fluorescent or epitope tag |
| Does overexpression of a lipid transporter increase uptake? | Overexpression cell model with quantitative lipid analysis |
| Which genes regulate lipid import in a genome-wide manner? | CRISPR library screening with lipid uptake readout |
How to Study the lipid import into cell Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescent lipid uptake assay | Rate and extent of lipid import | Comparing wild-type and knockout cells |
| Radiolabeled fatty acid flux | Oxidation and incorporation of imported fatty acids | Mitochondrial metabolism studies |
| Live-cell imaging | Dynamics of endocytic and trafficking events | Visualizing lipid delivery to organelles |
| CRISPR library screening | Genome-wide regulators of lipid import | Discovery of novel candidate genes |
| RNA-seq | Transcriptional response to lipid availability | Pathway and GO enrichment analysis |
| Proteomics | Protein abundance and interactions in lipid import | Identifying transport complexes |
| Seahorse respirometry | Mitochondrial oxidative capacity | Linking lipid import to energy metabolism |
| Calcium imaging | ER-mitochondria calcium transfer | Studying contact site function in adipocytes |
Lipid uptake and flux assays
Quantitative measurement of lipid import typically uses fluorescent or radiolabeled lipid analogs that are added to the extracellular medium and tracked over time. These assays can distinguish plasma membrane transport from endocytic uptake and can be combined with inhibitors to define the route of entry. Downstream flux into lipid droplets or mitochondria can be monitored to determine the fate of imported lipids.
Imaging of lipid trafficking
Fluorescence microscopy with lipid-binding dyes and tagged proteins allows visualization of lipid import and intracellular trafficking. Live-cell imaging can capture the dynamics of endocytic vesicles and the delivery of lipids to organelles such as mitochondria and lipid droplets. Contact site markers, such as those used to study Seipin, help resolve ER-mitochondria lipid and calcium exchange.
Omics and CRISPR screening
Transcriptomic and proteomic profiling can identify genes and pathways that respond to changes in lipid availability. CRISPR library screening enables unbiased discovery of regulators of lipid import by coupling gene perturbation to a lipid uptake readout. Bioinformatics integration of these datasets with GO:0140354 annotations helps prioritize candidate genes for functional validation.
Mitochondrial and metabolic readouts
Because imported lipids feed into mitochondrial metabolism, researchers often measure oxygen consumption, fatty acid oxidation and mitochondrial membrane composition. Stress conditions that alter mitochondrial permeability can be used to probe the coupling between lipid import and oxidative metabolism. These readouts are essential for linking lipid import to cellular energy homeostasis.
How CRISPR Can Be Used to Study GO:0140354 lipid import into cell
Knockout
CRISPR knockout is used to delete candidate lipid import genes and test whether lipid uptake is reduced or abolished. For example, knocking out SCARB1 or TAGLN2 can reveal their requirement for cholesterol uptake or T cell lipid metabolism, respectively. Knockout models are also valuable for validating hits from CRISPR library screens.
Point Mutation
Point-mutation knock-in allows researchers to test the function of specific residues within lipid transporters or regulatory proteins. This approach is useful for dissecting catalytic sites, post-translational modification sites and disease-associated variants. By introducing precise mutations, investigators can separate transport activity from protein stability or localization.
Knock-in
Knock-in of tags or reporter sequences enables visualization and purification of lipid import proteins at endogenous expression levels. Tagged knock-in models are particularly useful for studying proteins that localize to ER-mitochondria contact sites, such as Seipin. Knock-in of disease variants can also model how specific mutations affect lipid import in a physiological context.
Overexpression
Overexpression of lipid transporters or regulatory proteins can increase lipid import and reveal downstream consequences such as enhanced lipid storage or altered signalling. Overexpression models are often used in cancer research to mimic the upregulation of lipid uptake pathways observed in tumours. Combining overexpression with lipid flux assays provides a direct test of sufficiency.
How EDITGENE Supports lipid import into cell Research
Researchers studying lipid import into cell-related genes often need to determine whether a candidate gene is causally involved in lipid uptake, trafficking or downstream metabolism. Establishing causality requires precise genetic models that can remove, modify or amplify the gene of interest and then measure the functional consequences on lipid import and cellular physiology. EDITGENE provides a comprehensive suite of CRISPR-based services to generate such models efficiently and reproducibly.
Contact EDITGENE today to design your custom CRISPR model for lipid import into cell research.
Frequently Asked Questions About lipid import into cell
What is lipid import into cell (GO:0140354)?
It is the directed movement of a lipid from outside of a cell into a cell, which may occur via transport across the plasma membrane or via endocytosis.
What genes are involved in lipid import into cell?
Genes such as TAGLN2, SCARB1, ABCA1, IGF2BP3 and BSCL2 (Seipin) have been implicated in lipid uptake, trafficking and metabolism.
Why is lipid import important for cancer?
Lipid import supports the membrane and energy demands of tumour cells, and its reprogramming can promote immunosuppressive microenvironments.
How is lipid import into cell regulated?
It is regulated by extracellular lipid availability, expression of transport and endocytic machinery, mitochondrial metabolic demand and stress responses.
What is the difference between lipid import and lipid synthesis?
Lipid import refers to uptake from outside the cell, whereas lipid synthesis is the intracellular production of lipids; both contribute to cellular lipid pools.
Which organelles receive imported lipids?
Imported lipids are delivered to the endoplasmic reticulum, mitochondria and lipid droplets, among other compartments.
How can I study lipid import in the lab?
Common methods include fluorescent lipid uptake assays, radiolabeled flux measurements, imaging, omics and CRISPR screening.
What CRISPR models are used for lipid import research?
Knockout, point-mutation, knock-in, tagged knock-in and overexpression models are all used to dissect lipid import gene function.
Is lipid import linked to immune function?
Yes, Transgelin 2 guards T cell lipid metabolism and antitumour function, linking lipid handling to immune surveillance.
What diseases are associated with defective lipid import?
Cancer, metabolic disorders and mitochondrial dysfunction have been linked to altered lipid import and trafficking.
Conclusion
GO:0140354 lipid import into cell is a fundamental biological process that supplies cells with essential lipids for membrane biogenesis, energy production and signalling. Its molecular players, including TAGLN2, SCARB1 and Seipin, connect lipid uptake to immune function, cancer progression and metabolic regulation. Understanding the mechanisms, regulation and disease relevance of lipid import provides a rich framework for both basic and translational research. CRISPR-based models are indispensable for establishing causality in lipid import research, and services such as those offered by EDITGENE enable efficient generation of knockout, point-mutation, knock-in and overexpression cell models. By combining these models with functional lipid assays and bioinformatics, researchers can accelerate discovery in this important field.
References
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- 2. Horvath SE et al.. 2013. Lipids of mitochondria.. Prog Lipid Res 52(4):590-614 PMID: 24007978
- 3. Vance JE. 2015. Phospholipid synthesis and transport in mammalian cells.. Traffic 16(1):1-18 PMID: 25243850
- 4. Smolková K et al.. 2025. Fatty Acid Trafficking Between Lipid Droplets and Mitochondria: An Emerging Perspective.. Int J Biol Sci 21(5):1863-1873 PMID: 40083687
- 5. Wedan RJ et al.. 2024. Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.. Cell Metab 36(1):36-47 PMID: 38128528
- 6. Amen T et al.. 2021. Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability.. Cell Rep 35(11):109237 PMID: 34133922
- 7. Ning H et al.. 2025. CircABCA1 promotes ccRCC by reprogramming cholesterol metabolism and facilitating M2 macrophage polarization through IGF2BP3-mediated stabilization of SCARB1 mRNA.. Mol Cancer 24(1):199 PMID: 40684174
- 8. Combot Y et al.. 2022. Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes.. Cell Rep 38(2):110213 PMID: 35021082
