GO:0071447 cellular response to hydroperoxide: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071447 (cellular response to hydroperoxide) describes how a cell changes its state or activity in response to a hydroperoxide stimulus, where hydroperoxides are monosubstitution products of hydrogen peroxide (HOOH).
• Hydroperoxide sensing in plant cells is mediated by the hydrogen peroxide sensor HPCA1, an LRR receptor kinase that is activated by H2O2 and triggers downstream signaling.
• Peroxiredoxins are central enzymatic defenders against hydroperoxide stress, and their expression variants are dynamically regulated in response to hydroperoxide exposure.
• The fluorescent sensor roGFP2-Orp1 enables real-time monitoring of intracellular H2O2 dynamics and thiol redox integration during oxidative bursts.
• Hydroperoxide stress responses intersect with apoptosis regulation, as the deubiquitinase Usp18 prevents cellular apoptosis from oxidative stress in liver cells.
• Excessive mitochondrial hydrogen peroxide production contributes to atopic dermatitis, linking hydroperoxide biology to inflammatory skin disease.
Description
Cellular response to hydroperoxide (GO:0071447) is a biological process defined as any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydroperoxide stimulus, where hydroperoxides are monosubstitution products of hydrogen peroxide, HOOH. This term captures the full spectrum of cellular reactions to hydroperoxide exposure, from immediate sensing and signaling events to long-term transcriptional and metabolic adaptations. Understanding this response is critical because hydroperoxides are both normal byproducts of aerobic metabolism and potent signaling molecules that can cause oxidative damage when uncontrolled. Research into GO:0071447 has revealed that cells employ sophisticated detection systems, including the Arabidopsis LRR receptor kinase HPCA1, which directly senses hydrogen peroxide and initiates signaling cascades. The fluorescent protein sensor roGFP2-Orp1 has been instrumental in monitoring in vivo H2O2 dynamics and thiol redox integration during elicitor-induced oxidative bursts, providing spatial and temporal resolution of hydroperoxide signaling. These tools have established that hydroperoxide responses are not merely defensive but are integrated into developmental and immune programs. The importance of GO:0071447 extends to human health, where dysregulated hydroperoxide responses contribute to conditions such as atopic dermatitis, in which excessive mitochondrial hydrogen peroxide production drives disease pathology. Peroxiredoxins, which are key enzymes in hydroperoxide detoxification, show expression variants in response to hydroperoxide stress, indicating adaptive transcriptional programs. Furthermore, the deubiquitinase Usp18 protects liver cells from oxidative stress-induced apoptosis, demonstrating that hydroperoxide response pathways intersect with cell survival machinery. This article synthesizes the current understanding of GO:0071447, covering its definition, molecular mechanisms, key genes, disease relevance, and research methodologies.
cellular response to hydroperoxide At A Glance
| GO ID | GO:0071447 |
|---|---|
| GO term | cellular response to hydroperoxide |
| Ontology | biological_process |
| Synonym | none |
| Definition | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydroperoxide stimulus. Hydroperoxides are monosubstitution products of hydrogen peroxide, HOOH. |
| Major function | Detection, signaling, and adaptive cellular responses to hydroperoxide stress, including gene expression changes and detoxification. |
| Key sensors | HPCA1 (LRR receptor kinase) in plants; roGFP2-Orp1 used as a sensor for H2O2 dynamics. |
| Key effectors | Peroxiredoxins, Usp18. |
| Related disease examples | Atopic dermatitis, oxidative stress-induced apoptosis in liver cells. |
What Is GO:0071447?
GO:0071447, cellular response to hydroperoxide, is defined by QuickGO as any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydroperoxide stimulus. Hydroperoxides are monosubstitution products of hydrogen peroxide, HOOH. In practical terms, this GO term encompasses all cellular events triggered when a cell encounters a hydroperoxide molecule, including signal transduction, transcriptional reprogramming, enzyme activation, and metabolic adjustments.
Why Is cellular response to hydroperoxide Important in Cell Biology?
GO:0071447 is important because hydroperoxides are ubiquitous reactive oxygen species that can cause oxidative damage to lipids, proteins, and DNA, and cells must rapidly detect and respond to them to maintain homeostasis. The response involves both protective mechanisms, such as peroxiredoxin-mediated detoxification, and signaling roles that influence cell fate decisions including apoptosis and survival. In plants, hydroperoxide sensing by HPCA1 is critical for immune responses and stomatal closure. In humans, dysregulated hydroperoxide responses contribute to inflammatory skin diseases like atopic dermatitis. Thus, understanding this process has broad implications for cell biology, immunology, and disease therapy.
• Hydroperoxides are major oxidative stress agents that damage cellular components and must be detoxified.
• Peroxiredoxins, key enzymes in hydroperoxide response, show expression variants under hydroperoxide stress, indicating adaptive regulation.
• The plant receptor kinase HPCA1 directly senses hydrogen peroxide and mediates signaling, linking hydroperoxide response to immunity.
• Real-time monitoring of H2O2 dynamics via roGFP2-Orp1 reveals thiol redox integration during oxidative bursts.
• Usp18 prevents apoptosis from oxidative stress in liver cells, connecting hydroperoxide response to cell survival.
• Excessive mitochondrial hydrogen peroxide production contributes to atopic dermatitis pathogenesis.
• Organic hydroperoxide response in bacteria involves OhrR and affects virulence traits.
• AQP1 differentially orchestrates endothelial cell senescence, implicating hydroperoxide-related pathways in aging.
• Hydroperoxide response pathways are conserved from bacteria to plants to humans.
• Targeting hydroperoxide response genes offers therapeutic potential for oxidative stress-related diseases.
What Happens During cellular response to hydroperoxide?
Hydroperoxide sensing and signal initiation
In simple terms: Cells first detect hydroperoxides using specialized sensor proteins.
The cellular response to hydroperoxide begins with detection. In Arabidopsis, the LRR receptor kinase HPCA1 functions as a hydrogen peroxide sensor that is activated by H2O2 and initiates downstream signaling. This sensing mechanism is essential for triggering rapid cellular changes. The fluorescent sensor roGFP2-Orp1 has been used to monitor in vivo H2O2 dynamics and thiol redox integration during elicitor-induced oxidative bursts, revealing that hydroperoxide signals are spatially and temporally controlled. These sensing events represent the earliest stage of GO:0071447.
Transcriptional reprogramming
In simple terms: Cells change which genes they express to cope with hydroperoxide stress.
Following detection, cells undergo extensive changes in gene expression. Variants of peroxiredoxins, which are antioxidant enzymes, show altered expression in response to hydroperoxide stress, indicating a transcriptional adaptive response. In the bacterium Chromobacterium violaceum, the global transcriptional response to organic hydroperoxide is controlled in part by the regulator OhrR, which also influences virulence traits. These examples demonstrate that GO:0071447 includes coordinated changes in the transcriptome that help cells manage hydroperoxide challenges.
Enzymatic detoxification by peroxiredoxins
In simple terms: Special enzymes break down hydroperoxides to protect the cell.
A central component of the hydroperoxide response is the enzymatic reduction of hydroperoxides by peroxiredoxins. Mitochondrial peroxiredoxins are key enzymes that detoxify hydroperoxides and regulate redox signaling. Their expression is dynamically regulated under hydroperoxide stress, as shown by the identification of peroxiredoxin variants. This detoxification system is conserved and critical for limiting oxidative damage during GO:0071447.
Integration with cell survival and apoptosis pathways
In simple terms: The hydroperoxide response can decide whether a cell lives or dies.
The cellular response to hydroperoxide intersects with apoptosis machinery. The deubiquitinase Usp18 prevents cellular apoptosis from oxidative stress in liver cells, indicating that hydroperoxide signaling can be modulated by ubiquitin-related processes. This integration ensures that cells can either repair damage or undergo programmed cell death if stress is overwhelming. Thus, GO:0071447 encompasses cross-talk with cell fate pathways.
Physiological and pathological outcomes
In simple terms: The response can lead to both protection and disease, depending on context.
The ultimate outcomes of GO:0071447 vary. In atopic dermatitis, excessive production of hydrogen peroxide in mitochondria contributes to disease pathology, highlighting that dysregulated hydroperoxide responses can be harmful. Conversely, in plants, HPCA1-mediated sensing is required for proper immune responses. Additionally, AQP1 differentially orchestrates endothelial cell senescence, linking hydroperoxide-related processes to aging. These examples illustrate the broad physiological and pathological consequences of the cellular response to hydroperoxide.
Key Genes Involved in GO:0071447 cellular response to hydroperoxide
The following genes and proteins are experimentally implicated in the cellular response to hydroperoxide (GO:0071447) based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HPCA1 | Hydrogen peroxide sensor LRR receptor kinase in Arabidopsis | Mediates H2O2 sensing and downstream signaling; key for plant immunity |
| Orp1 (roGFP2-Orp1) | Fusion sensor for H2O2 and thiol redox | Enables real-time monitoring of intracellular H2O2 dynamics |
| Peroxiredoxins (mitochondrial) | Detoxify hydroperoxides | Central enzymes in hydroperoxide reduction and redox signaling |
| Peroxiredoxin variants | Show altered expression under hydroperoxide stress | Indicate adaptive transcriptional response to hydroperoxides |
| Usp18 | Deubiquitinase preventing apoptosis from oxidative stress | Links hydroperoxide response to cell survival in liver cells |
| OhrR | Regulator of organic hydroperoxide response | Controls virulence traits in Chromobacterium violaceum |
| Mitochondrial H2O2 production (e.g., complex I/III) | Source of excessive H2O2 in atopic dermatitis | Contributes to inflammatory skin disease |
| AQP1 | Aquaporin orchestrating endothelial cell senescence | Implicated in hydroperoxide-related aging processes |
| HPCA1 homologs (human) | Potential H2O2 sensors (not directly verified in cited list) | May be explored in future studies |
| Peroxiredoxin 3 (PRDX3) | Mitochondrial peroxiredoxin | Protects mitochondria from hydroperoxide damage |
| Peroxiredoxin 5 (PRDX5) | Mitochondrial peroxiredoxin | Contributes to hydroperoxide detoxification |
| Thioredoxin (Trx) | Electron donor for peroxiredoxins | Supports peroxiredoxin activity |
| Thioredoxin reductase | Regenerates reduced thioredoxin | Maintains peroxiredoxin function |
| Glutathione peroxidase | Alternative hydroperoxide detoxification enzyme (not directly cited) | Potential backup system |
| Catalase | Decomposes hydrogen peroxide (not directly cited) | Indirectly related to hydroperoxide response |
| Superoxide dismutase | Converts superoxide to H2O2 (not directly cited) | Upstream of hydroperoxide generation |
| Nrf2 (NFE2L2) | Master regulator of antioxidant response (not directly cited) | Potential downstream target |
| Ohr (organic hydroperoxide resistance protein) | Enzyme in bacteria (not directly cited) | Related to OhrR regulon |
How Is cellular response to hydroperoxide Regulated?
The cellular response to hydroperoxide (GO:0071447) is regulated at multiple levels. In plants, HPCA1-mediated sensing initiates signaling, and the response is integrated with immune pathways. The roGFP2-Orp1 sensor studies have shown that H2O2 dynamics during oxidative bursts are tightly controlled, indicating regulation of production and scavenging. Peroxiredoxin expression is dynamically regulated under hydroperoxide stress, suggesting transcriptional control. In bacteria, OhrR regulates the organic hydroperoxide response and virulence traits. In mammalian cells, Usp18 modulates apoptosis under oxidative stress, providing a regulatory node. Additionally, mitochondrial H2O2 production is a regulated process that can become excessive in disease. These layers of regulation ensure appropriate cellular outcomes.
cellular response to hydroperoxide and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Mitochondrial H2O2 production | Atopic dermatitis | Keratinocyte or skin equivalent models with modulated mitochondrial ROS |
| Usp18 | Liver apoptosis from oxidative stress | Usp18 knockout or overexpression in hepatocytes |
| AQP1 | Endothelial senescence | AQP1 knockout or overexpression in endothelial cells |
| OhrR | Bacterial virulence | OhrR mutant in Chromobacterium violaceum |
| Peroxiredoxins | Oxidative stress-related diseases | Peroxiredoxin knockout or knockdown cells |
Atopic dermatitis
Excessive production of hydrogen peroxide in mitochondria contributes to atopic dermatitis, a chronic inflammatory skin disease. This links dysregulated hydroperoxide metabolism to disease pathogenesis. The cellular response to hydroperoxide (GO:0071447) may be overwhelmed or maladaptive in this context, leading to skin barrier dysfunction and inflammation.
Liver injury and apoptosis
In liver cells, oxidative stress can trigger apoptosis, and the deubiquitinase Usp18 prevents this process. This indicates that the cellular response to hydroperoxide is critical for determining cell fate in the liver. Dysregulation of such protective mechanisms may contribute to liver injury and disease progression.
Endothelial senescence and aging
AQP1 differentially orchestrates endothelial cell senescence, a process linked to aging and cardiovascular disease. While the exact connection to hydroperoxide response is not fully defined in the cited study, it suggests that aquaporins may influence redox balance and senescence. Further research could clarify the role of GO:0071447 in vascular aging.
Bacterial virulence
In Chromobacterium violaceum, the organic hydroperoxide response regulator OhrR controls virulence traits. This demonstrates that hydroperoxide response pathways can impact host-pathogen interactions. Understanding GO:0071447 in bacteria may inform strategies against infectious diseases.
From cellular response to hydroperoxide-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X sense hydroperoxides? | Knockout of candidate sensor (e.g., HPCA1) followed by H2O2 treatment |
| How does gene X affect hydroperoxide-induced apoptosis? | Point mutation or knockout of Usp18 in liver cells |
| What is the transcriptional response to hydroperoxide? | RNA-seq of cells with peroxiredoxin variants |
| Can we visualize H2O2 dynamics in real time? | Knock-in of roGFP2-Orp1 sensor |
| Does overexpression of gene X protect against hydroperoxide stress? | Overexpression of peroxiredoxins or Usp18 |
| Does gene X regulate virulence via hydroperoxide response? | OhrR knockout in Chromobacterium violaceum |
How to Study the cellular response to hydroperoxide Process
| Method | What It Measures | Typical Application |
|---|---|---|
| roGFP2-Orp1 imaging | Intracellular H2O2 dynamics and thiol redox | Monitoring oxidative bursts in live cells |
| RNA-seq | Global transcriptional changes | Identifying hydroperoxide-responsive genes |
| Redox proteomics | Protein thiol oxidation states | Detecting peroxiredoxin oxidation |
| Knockout models | Loss-of-function effects | Testing necessity of genes in hydroperoxide response |
| Overexpression models | Gain-of-function effects | Testing sufficiency of protective genes |
| Apoptosis assays | Cell death rates | Evaluating hydroperoxide-induced apoptosis |
| Bacterial virulence assays | Virulence traits | Studying OhrR regulon in Chromobacterium violaceum |
| Mitochondrial H2O2 measurement | Mitochondrial ROS production | Linking mitochondrial H2O2 to atopic dermatitis |
Genetically encoded fluorescent sensors
The roGFP2-Orp1 sensor allows real-time monitoring of intracellular H2O2 dynamics and thiol redox integration in living cells. This method is ideal for studying the temporal and spatial aspects of GO:0071447, especially during oxidative bursts.
Transcriptomics (RNA-seq)
RNA sequencing can reveal global transcriptional changes in response to hydroperoxide stress. For example, peroxiredoxin variants show altered expression under hydroperoxide stress, and OhrR regulates a large regulon in bacteria. This approach identifies genes and pathways involved in GO:0071447.
Proteomics and redox proteomics
Proteomic methods can quantify changes in protein abundance and oxidation states. Peroxiredoxins are key targets, and their oxidation status can be monitored to assess hydroperoxide response. Redox proteomics can identify proteins with altered thiol oxidation during GO:0071447.
Genetic knockout and overexpression
Knockout or overexpression of candidate genes such as Usp18 or peroxiredoxins can test their causal roles in hydroperoxide response. These models are essential for linking specific genes to GO:0071447 phenotypes.
How CRISPR Can Be Used to Study GO:0071447 cellular response to hydroperoxide
Knockout
CRISPR knockout can generate cell lines lacking candidate genes such as HPCA1, Usp18, or peroxiredoxins to test their necessity in the cellular response to hydroperoxide. For example, Usp18 knockout liver cells would be expected to show increased apoptosis under oxidative stress.
Point Mutation
Point mutations can be introduced to dissect specific domains or catalytic residues. For instance, mutating the kinase domain of HPCA1 could clarify its role in H2O2 sensing. Similarly, point mutations in peroxiredoxin active sites can reveal their catalytic mechanism.
Knock-in
Knock-in of fluorescent sensors like roGFP2-Orp1 allows real-time monitoring of H2O2 dynamics in a native context. This approach can be used to study GO:0071447 with high spatial and temporal resolution.
Overexpression
CRISPR activation or cDNA overexpression can elevate levels of protective genes such as Usp18 or peroxiredoxins to test whether they confer resistance to hydroperoxide stress. This is useful for identifying therapeutic targets.
How EDITGENE Supports cellular response to hydroperoxide Research
Researchers studying cellular response to hydroperoxide-related genes often need to determine whether a candidate gene is causally involved in sensing, detoxification, or downstream signaling. EDITGENE provides comprehensive CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for cellular response to hydroperoxide research.
Frequently Asked Questions About cellular response to hydroperoxide
What is GO:0071447?
GO:0071447 is the Gene Ontology term for cellular response to hydroperoxide, defined as any process that results in a change in state or activity of a cell as a result of a hydroperoxide stimulus.
What are hydroperoxides?
Hydroperoxides are monosubstitution products of hydrogen peroxide, HOOH, and can act as signaling molecules or cause oxidative damage.
What genes are involved in cellular response to hydroperoxide?
Key genes include HPCA1, peroxiredoxins, Usp18, OhrR, and AQP1.
How do cells sense hydroperoxides?
In plants, the LRR receptor kinase HPCA1 senses hydrogen peroxide. Fluorescent sensors like roGFP2-Orp1 allow monitoring of H2O2 dynamics.
What is the role of peroxiredoxins in hydroperoxide response?
Peroxiredoxins are enzymes that detoxify hydroperoxides and show altered expression under hydroperoxide stress.
How is cellular response to hydroperoxide studied?
Methods include genetically encoded sensors, RNA-seq, proteomics, and CRISPR knockout models.
What diseases are linked to hydroperoxide response?
Atopic dermatitis, liver apoptosis, and endothelial senescence are associated with hydroperoxide-related processes.
Can CRISPR be used to study GO:0071447?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools to dissect gene function in this process.
What is the difference between hydrogen peroxide and hydroperoxide?
Hydroperoxides are monosubstitution products of hydrogen peroxide, meaning one hydrogen atom is replaced by another group.
Why is cellular response to hydroperoxide important?
It protects cells from oxidative damage and regulates signaling, with implications for immunity, aging, and disease.
Conclusion
GO:0071447, cellular response to hydroperoxide, is a fundamental biological process that enables cells to detect and respond to hydroperoxide stimuli. Research has identified key sensors like HPCA1, detoxifying enzymes such as peroxiredoxins, and regulatory proteins like Usp18. Dysregulation of this response contributes to diseases including atopic dermatitis and liver injury. Advanced tools like roGFP2-Orp1 and CRISPR-based models are accelerating discoveries in this field. EDITGENE offers comprehensive services to support researchers investigating this critical pathway.
References
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- 2. Wu F et al.. 2020. Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis.. Nature 578(7796):577-581 PMID: 32076270
- 3. Nietzel T et al.. 2019. The fluorescent protein sensor roGFP2-Orp1 monitors in vivo H(2) O(2) and thiol redox integration and elucidates intracellular H(2) O(2) dynamics during elicitor-induced oxidative burst in Arabidopsis.. New Phytol 221(3):1649-1664 PMID: 30347449
- 4. Cao Z et al.. 2007. Mitochondrial peroxiredoxins.. Subcell Biochem 44:295-315 PMID: 18084900
- 5. Mitsumoto A et al.. 2001. Variants of peroxiredoxins expression in response to hydroperoxide stress.. Free Radic Biol Med 30(6):625-35 PMID: 11295360
- 6. Lai KP et al.. 2017. Deubiquitinase Usp18 prevents cellular apoptosis from oxidative stress in liver cells.. Cell Biol Int 41(8):914-921 PMID: 28557172
- 7. Previato-Mello M et al.. 2017. Global Transcriptional Response to Organic Hydroperoxide and the Role of OhrR in the Control of Virulence Traits in Chromobacterium violaceum.. Infect Immun 85(8) PMID: 28507067
- 8. Minzaghi D et al.. 2023. Excessive Production of Hydrogen Peroxide in Mitochondria Contributes to Atopic Dermatitis.. J Invest Dermatol 143(10):1906-1918.e8 PMID: 37085042
