GO:1903965 monounsaturated fatty acid catabolic process: Lipid Breakdown Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1903965 describes the biological process that breaks down monounsaturated fatty acids (MUFAs) into acetyl-CoA and other metabolites for energy production and membrane lipid remodeling.
• Key enzymes include SCD1, which desaturates saturated fatty acids to generate MUFAs, and downstream beta-oxidation enzymes that catabolize them.
• MUFA catabolism is critical for maintaining lipid homeostasis, and its dysregulation is linked to obesity-related inflammation, cancer progression, and metabolic disorders.
• Exogenous MUFAs can promote a ferroptosis-resistant cell state, highlighting the interplay between MUFA metabolism and cell death pathways.
• In hepatocellular carcinoma, dietary MUFAs facilitate lipid droplet turnover through HSP90A-mediated lysosomal degradation of PLIN2, linking MUFA catabolism to autophagy.
• CRISPR-Cas9 knockout of GmPDCTs in soybean increased monounsaturated fatty acid content, demonstrating the agricultural relevance of MUFA catabolic pathways.
Description
Monounsaturated fatty acid catabolic process (GO:1903965) is a biological process defined as the chemical reactions and pathways resulting in the breakdown of monounsaturated fatty acids. Monounsaturated fatty acids (MUFAs) are fatty acids with a single double bond in their carbon chain, such as oleic acid and palmitoleic acid. Their catabolism is essential for energy production, membrane lipid remodeling, and cellular signaling. This process is particularly relevant in metabolic tissues like adipose tissue, liver, and muscle, where MUFA breakdown contributes to overall lipid homeostasis. Research has shown that MUFA catabolism intersects with critical cellular pathways, including autophagy, ferroptosis, and mitochondrial function. For example, Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes, indicating that MUFA metabolism is tightly linked to cell survival mechanisms. In cancer, CD36-mediated uptake of MUFAs maintains lipid homeostasis during matrix detachment and tumor progression, underscoring the importance of MUFA catabolism in cancer cell adaptation. Understanding GO:1903965 is therefore crucial for researchers studying metabolic diseases, cancer, and neurodegenerative conditions. The process involves a complex network of enzymes, transporters, and regulatory proteins that are potential therapeutic targets. This article provides a comprehensive overview of the genes, mechanisms, and research methods associated with monounsaturated fatty acid catabolic process, based on authoritative QuickGO data and verified PubMed literature.
monounsaturated fatty acid catabolic process At A Glance
| GO ID | GO:1903965 |
|---|---|
| GO term | monounsaturated fatty acid catabolic process |
| Ontology | biological_process |
| Synonym | monounsaturated fatty acid breakdown, monounsaturated fatty acid catabolism, monounsaturated fatty acid degradation |
| Major function | Breakdown of monounsaturated fatty acids for energy production and lipid homeostasis |
| Related pathways | Beta-oxidation, autophagy, ferroptosis, lipid droplet turnover |
| Key enzymes | SCD1, acyl-CoA dehydrogenases, CD36, HSP90A |
| Cellular locations | Mitochondria, peroxisomes, lysosomes, cytoplasm |
What Is GO:1903965?
Monounsaturated fatty acid catabolic process (GO:1903965) is the set of chemical reactions and pathways that result in the breakdown of monounsaturated fatty acids. This process typically begins with the activation of MUFAs to fatty acyl-CoA derivatives, followed by their transport into mitochondria or peroxisomes, where beta-oxidation sequentially removes two-carbon units to generate acetyl-CoA, NADH, and FADH2. The acetyl-CoA then enters the tricarboxylic acid cycle for further energy production. In addition to energy generation, MUFA catabolism provides precursors for membrane lipid synthesis and signaling molecules. The process is regulated by enzymes such as acyl-CoA dehydrogenases and auxiliary proteins that ensure efficient substrate channeling and metabolic flux.
Why Is monounsaturated fatty acid catabolic process Important in Cell Biology?
Monounsaturated fatty acid catabolic process is fundamentally important because it governs energy balance and lipid homeostasis in cells. Dysregulation of this process contributes to obesity, insulin resistance, and inflammation, as MUFAs and their catabolic products modulate signaling pathways. In cancer, MUFA catabolism supports tumor progression by maintaining lipid homeostasis during matrix detachment and providing energy for rapid proliferation. Moreover, MUFAs can protect cells from ferroptosis, a form of iron-dependent cell death, by altering membrane lipid composition. In neurodegenerative conditions such as adrenomyeloneuropathy, nervonic acid, a long-chain MUFA, improves mitochondrial function, suggesting that MUFA catabolism is relevant to neuronal health. Thus, understanding GO:1903965 offers insights into metabolic diseases, cancer, and neurodegeneration.
• Regulates energy production through beta-oxidation of MUFAs.
• Maintains lipid homeostasis and membrane fluidity.
• Modulates ferroptosis sensitivity, impacting cancer cell survival.
• Links to autophagy and adipocyte survival via Scd1 and MUFA lipids.
• Involved in obesity-related inflammation and metabolic syndrome.
• Supports tumor progression by maintaining lipid homeostasis during matrix detachment.
• Nervonic acid, a MUFA, improves mitochondrial function in adrenomyeloneuropathy.
• Dietary MUFAs facilitate lipid droplet turnover in hepatocellular carcinoma.
• CRISPR-Cas9 knockout of GmPDCTs increases MUFA content in soybean oil.
• Provides targets for therapeutic intervention in metabolic disorders and cancer.
What Happens During monounsaturated fatty acid catabolic process?
Activation and Transport of MUFAs
In simple terms: First, monounsaturated fatty acids are activated and shuttled to the places where they are broken down.
Monounsaturated fatty acids are first activated to fatty acyl-CoA derivatives by acyl-CoA synthetases. These activated MUFAs are then transported into mitochondria or peroxisomes via carnitine palmitoyltransferase systems. CD36, a fatty acid translocase, facilitates the selective uptake of MUFAs, as shown in cancer cells during matrix detachment. This step ensures that MUFAs are available for catabolism and is a key regulatory point in the process.
Beta-Oxidation Cycle
In simple terms: The fatty acid chain is chopped into two-carbon units, releasing energy.
Inside mitochondria or peroxisomes, MUFAs undergo beta-oxidation, a cycle of four reactions: dehydrogenation, hydration, dehydrogenation, and thiolysis. Each cycle removes two carbons as acetyl-CoA, generating NADH and FADH2. This process is catalyzed by acyl-CoA dehydrogenases and other enzymes. The acetyl-CoA enters the TCA cycle for ATP production. Scd1, which desaturates saturated fatty acids to MUFAs, is required for autophagy and survival of adipocytes, indicating that MUFA catabolism is linked to cellular stress responses.
Lysosomal Degradation of Lipid Droplets
In simple terms: Fat droplets in cells can be broken down in lysosomes, a process aided by chaperones.
In hepatocellular carcinoma, dietary monounsaturated fatty acids facilitate lipid droplet turnover through chaperone HSP90A-mediated lysosomal degradation of PLIN2. This pathway represents an alternative route for MUFA catabolism, where lipid droplets are delivered to lysosomes for degradation. This process is important for cancer cell survival under metabolic stress.
Regulation by Autophagy and Ferroptosis
In simple terms: The breakdown of MUFAs is connected to cell survival and death programs.
Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state by altering membrane lipid composition, which reduces lipid peroxidation. Conversely, Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes, suggesting that MUFA catabolism supports autophagic flux. These interactions highlight the crosstalk between MUFA catabolism and cell death/survival pathways.
Mitochondrial Function and Energy Homeostasis
In simple terms: Breaking down MUFAs helps mitochondria work properly and maintain energy balance.
Nervonic acid, a long-chain monounsaturated fatty acid, improves mitochondrial function in adrenomyeloneuropathy fibroblasts, indicating that MUFA catabolism supports mitochondrial respiration and energy homeostasis. This is particularly relevant in neurodegenerative diseases where mitochondrial dysfunction is a hallmark.
Key Genes Involved in GO:1903965 monounsaturated fatty acid catabolic process
The following genes and proteins are key players in monounsaturated fatty acid catabolic process, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SCD1 | Desaturates saturated fatty acids to monounsaturated fatty acids | Required for autophagy and survival of adipocytes |
| CD36 | Facilitates selective uptake of monounsaturated fatty acids | Maintains lipid homeostasis during matrix detachment and tumor progression |
| HSP90A | Chaperone mediating lysosomal degradation of PLIN2 | Facilitates lipid droplet turnover in hepatocellular carcinoma |
| PLIN2 | Lipid droplet-associated protein | Target of HSP90A-mediated degradation in MUFA-induced lipid droplet turnover |
| ACADM | Medium-chain acyl-CoA dehydrogenase | Catalyzes beta-oxidation of MUFAs |
| ACADL | Long-chain acyl-CoA dehydrogenase | Catalyzes beta-oxidation of MUFAs |
| CPT1A | Carnitine palmitoyltransferase 1A | Transports MUFAs into mitochondria for beta-oxidation |
| CPT2 | Carnitine palmitoyltransferase 2 | Transports MUFAs into mitochondria for beta-oxidation |
| ACOX1 | Peroxisomal acyl-CoA oxidase 1 | Catalyzes peroxisomal beta-oxidation of MUFAs |
| EHHADH | Enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase | Peroxisomal beta-oxidation of MUFAs |
| HADHA | Mitochondrial trifunctional protein alpha subunit | Catalyzes beta-oxidation of MUFAs |
| HADHB | Mitochondrial trifunctional protein beta subunit | Catalyzes beta-oxidation of MUFAs |
| GmPDCTs | Phosphatidylcholine:diacylglycerol cholinephosphotransferase | Knockout increases monounsaturated fatty acid content in soybean oil |
| FABP4 | Fatty acid binding protein 4 | Binds and transports MUFAs in adipocytes |
| LPL | Lipoprotein lipase | Hydrolyzes triglycerides to release MUFAs |
| PPARA | Peroxisome proliferator-activated receptor alpha | Regulates expression of MUFA catabolic genes |
| NR1H3 | Liver X receptor alpha | Regulates lipid homeostasis and MUFA catabolism |
How Is monounsaturated fatty acid catabolic process Regulated?
Monounsaturated fatty acid catabolic process is regulated at multiple levels. Transcriptional regulation involves nuclear receptors such as PPARA and NR1H3, which control the expression of genes encoding beta-oxidation enzymes and transporters. Post-translational regulation includes phosphorylation of acyl-CoA dehydrogenases and carnitine palmitoyltransferases, which modulates their activity. Additionally, the process is influenced by nutrient availability and hormonal signals, such as insulin and glucagon. In cancer, CD36-mediated uptake of MUFAs is regulated by matrix detachment, ensuring lipid homeostasis during tumor progression. Furthermore, HSP90A-mediated lysosomal degradation of PLIN2 is a regulatory mechanism for lipid droplet turnover in response to dietary MUFAs. Autophagy and ferroptosis pathways also intersect with MUFA catabolism, providing additional layers of regulation.
monounsaturated fatty acid catabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CD36 | Cancer progression and metastasis | CD36 knockout cancer cell lines |
| HSP90A | Hepatocellular carcinoma | HSP90A knockout or knockdown in HCC cells |
| SCD1 | Obesity and adipocyte survival | Scd1 knockout mice or adipocyte-specific knockout |
| Nervonic acid pathway | Adrenomyeloneuropathy | Patient-derived fibroblasts treated with nervonic acid |
| GmPDCTs | Soybean oil composition | CRISPR-Cas9 knockout in soybean |
Cancer and Tumor Progression
Monounsaturated fatty acid catabolic process plays a critical role in cancer. CD36 maintains lipid homeostasis via selective uptake of MUFAs during matrix detachment and tumor progression, allowing cancer cells to survive metabolic stress. In hepatocellular carcinoma, dietary MUFAs facilitate lipid droplet turnover through HSP90A-mediated lysosomal degradation of PLIN2, supporting cancer cell survival. Additionally, exogenous MUFAs promote a ferroptosis-resistant cell state, which can contribute to therapy resistance. These findings suggest that targeting MUFA catabolism could be a therapeutic strategy in cancer.
Obesity and Metabolic Inflammation
Dysregulation of monounsaturated fatty acid catabolic process is linked to obesity-related inflammation. MUFAs modulate inflammatory pathways, and their catabolism influences adipose tissue function. Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes, and their deficiency leads to adipocyte death and metabolic dysfunction. Thus, MUFA catabolism is a key determinant of metabolic health.
Neurodegeneration and Mitochondrial Function
In adrenomyeloneuropathy, nervonic acid, a long-chain monounsaturated fatty acid, improves mitochondrial function in patient fibroblasts. This suggests that MUFA catabolism supports mitochondrial respiration and may be protective in neurodegenerative conditions. Defects in MUFA catabolism could contribute to mitochondrial dysfunction observed in these diseases.
From monounsaturated fatty acid catabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate MUFA catabolism? | CRISPR knockout cell line (e.g., HepG2, HEK293T) |
| Does a point mutation in gene X affect enzyme activity? | CRISPR point mutation knock-in cell line |
| Does overexpression of gene X increase MUFA breakdown? | CRISPR overexpression cell line |
| Does tagging gene X affect its localization? | CRISPR tagged knock-in cell line |
| Does gene X knockout alter lipid droplet turnover? | CRISPR knockout in hepatocellular carcinoma cells |
| Does gene X knockout affect ferroptosis sensitivity? | CRISPR knockout in cancer cell lines treated with ferroptosis inducers |
How to Study the monounsaturated fatty acid catabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics (LC-MS) | Quantification of MUFA species and intermediates | Validation of knockout/overexpression effects on MUFA catabolism |
| Seahorse XF | Mitochondrial respiration and glycolysis | Assessment of energy production from MUFA catabolism |
| Confocal microscopy | Lipid droplet dynamics and protein localization | Visualization of PLIN2 degradation and lipid droplet turnover |
| CRISPR screen | Identification of genes regulating MUFA catabolism | Discovery of novel targets in cancer metabolism |
| RNA-seq | Transcriptional changes in MUFA catabolic genes | Analysis of regulatory networks |
| Western blot | Protein expression of beta-oxidation enzymes | Validation of knockout or overexpression |
| Autophagy flux assay | Autophagic activity | Linking MUFA catabolism to autophagy |
| Ferroptosis assay | Cell death sensitivity to ferroptosis inducers | Evaluating MUFA-mediated ferroptosis resistance |
Lipidomics and Mass Spectrometry
Lipidomics using mass spectrometry is essential for quantifying monounsaturated fatty acid levels and their catabolic intermediates. This method can measure changes in MUFA species in cells or tissues upon genetic manipulation. It is typically applied to validate knockout or overexpression models.
Seahorse XF Analyzer
The Seahorse XF analyzer measures mitochondrial respiration and glycolysis in live cells. It is used to assess the impact of MUFA catabolism on oxidative phosphorylation and energy production. This method is particularly useful for studying genes involved in beta-oxidation.
Confocal Microscopy and Live-Cell Imaging
Confocal microscopy with fluorescently tagged lipid droplets or proteins (e.g., PLIN2) allows visualization of lipid droplet dynamics and lysosomal degradation. Live-cell imaging can track MUFA-induced lipid droplet turnover in real time.
CRISPR Screening and Bioinformatics
Genome-wide CRISPR knockout screens combined with lipidomics or fluorescence-activated cell sorting can identify novel regulators of MUFA catabolism. Bioinformatics analysis of transcriptomic data can reveal pathways co-regulated with MUFA catabolic genes.
How CRISPR Can Be Used to Study GO:1903965 monounsaturated fatty acid catabolic process
Knockout
CRISPR-Cas9 knockout is used to completely ablate genes involved in monounsaturated fatty acid catabolic process, such as SCD1, CD36, or HSP90A. This allows researchers to determine the loss-of-function effects on MUFA breakdown, lipid homeostasis, and cell survival. For example, GmPDCTs knockout in soybean increased MUFA content, demonstrating the utility of CRISPR in agricultural biotechnology.
Point Mutation
CRISPR point mutation knock-in introduces specific amino acid substitutions to study the catalytic activity or regulatory sites of enzymes in MUFA catabolism. This is useful for dissecting the function of residues in acyl-CoA dehydrogenases or carnitine palmitoyltransferases.
Knock-in
CRISPR knock-in can be used to insert tags (e.g., GFP, HA) into endogenous genes to track protein localization and interactions in live cells. Tagged knock-in of PLIN2 or HSP90A enables real-time imaging of lipid droplet turnover.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression is used to increase the expression of genes involved in MUFA catabolism, such as SCD1 or CPT1A. This helps to study gain-of-function effects on lipid metabolism and energy production.
How EDITGENE Supports monounsaturated fatty acid catabolic process Research
Researchers studying monounsaturated fatty acid catabolic process-related genes often need to determine whether a candidate gene is causally involved in lipid breakdown, energy homeostasis, or disease progression. EDITGENE provides a comprehensive suite of CRISPR services to accelerate this research, from knockout to precise point mutations and overexpression models.
Contact EDITGENE today to design your custom CRISPR model for monounsaturated fatty acid catabolic process research.
Frequently Asked Questions About monounsaturated fatty acid catabolic process
What is monounsaturated fatty acid catabolic process?
It is the biological process (GO:1903965) that breaks down monounsaturated fatty acids into acetyl-CoA and other metabolites for energy production and lipid homeostasis.
What genes are involved in monounsaturated fatty acid catabolic process?
Key genes include SCD1, CD36, HSP90A, PLIN2, and beta-oxidation enzymes such as ACADM and CPT1A.
How is monounsaturated fatty acid catabolic process regulated?
It is regulated transcriptionally by PPARA and NR1H3, and post-translationally by phosphorylation and nutrient signals.
What diseases are associated with monounsaturated fatty acid catabolic process?
Dysregulation is linked to cancer, obesity-related inflammation, and neurodegeneration such as adrenomyeloneuropathy.
How can I study monounsaturated fatty acid catabolic process using CRISPR?
CRISPR knockout, point mutation, knock-in, and overexpression models can be used to dissect gene function in this pathway.
What is the role of CD36 in monounsaturated fatty acid catabolism?
CD36 facilitates selective uptake of monounsaturated fatty acids, maintaining lipid homeostasis during matrix detachment and tumor progression.
How does SCD1 affect monounsaturated fatty acid catabolism?
SCD1 desaturates saturated fatty acids to monounsaturated fatty acids, and its activity is required for autophagy and survival of adipocytes.
What is the connection between monounsaturated fatty acid catabolism and ferroptosis?
Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state by altering membrane lipid composition.
Can monounsaturated fatty acid catabolism be targeted for cancer therapy?
Yes, targeting MUFA catabolism pathways, such as CD36-mediated uptake or HSP90A-mediated lipid droplet turnover, is a potential therapeutic strategy.
What methods are used to measure monounsaturated fatty acid catabolic process?
Lipidomics, Seahorse XF, confocal microscopy, and CRISPR screens are commonly used to study this process.
Conclusion
Monounsaturated fatty acid catabolic process (GO:1903965) is a vital biological pathway that governs energy production, lipid homeostasis, and cell survival. Its dysregulation contributes to cancer, obesity, and neurodegeneration, making it a promising target for therapeutic intervention. Advances in CRISPR gene editing and lipidomics have accelerated our understanding of the genes and mechanisms involved. EDITGENE provides comprehensive CRISPR services to support research on this pathway, from knockout to overexpression models and library screening.
References
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- 3. Terry AR et al.. 2023. CD36 maintains lipid homeostasis via selective uptake of monounsaturated fatty acids during matrix detachment and tumor progression.. Cell Metab 35(11):2060-2076.e9 PMID: 37852255
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- 5. Mori H et al.. 2024. Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes.. Mol Metab 83:101916 PMID: 38492843
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- 8. Li H et al.. 2023. Design of high-monounsaturated fatty acid soybean seed oil using GmPDCTs knockout via a CRISPR-Cas9 system.. Plant Biotechnol J 21(7):1317-1319 PMID: 37084283
