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PubMed2026

Characterization of oxidative status in maize protoplasts under temperature and saline-alkali stresses.

BACKGROUND: Protoplasts have emerged as a powerful model system in plant functional genomics, offering significant utility in functional gene analysis, protein interaction studies, and transient expression platforms for gene editing. Despite their versatility, inherent limitations restrict their broader application, highlighting the need for systematic investigations into their responses to abiotic stressors, such as temperature fluctuations and saline-alkali conditions (200 mM saline mixture: 170mM NaCl and 30mM Na2CO3, pH = 9.1). RESULTS: In this study, we comprehensively examined the effects of varying temperatures and saline-alkali stress on the integrity, viability, and reactive oxygen species (ROS) metabolism of maize protoplasts. Key markers of oxidative stress-including ROS accumulation, lipid peroxidation (measured as malondialdehyde, MDA), antioxidant enzyme activity (superoxide dismutase, SOD), and hydrogen peroxide (H2O2) levels-were quantified to assess the oxidative stress response. Protoplasts maintained at 4 °C demonstrated enhanced stability and antioxidant capacity, preserving cell viability and endogenous protein integrity for up to 16 h. Conversely, exposure to 37 °C significantly compromised protoplast viability, while incubation at 28 °C exerted minimal effects within 16 h. CONCLUSIONS: Our study investigated the effects of various temperature stresses and salt-alkali stress on maize protoplasts. The results demonstrated that both temperature and salt-alkali stress significantly impacted protoplast production, viability, and the expression of endogenous proteins. These findings not only characterize the redox response of maize protoplasts, but also provide guidance for protoplast isolation and other procedures: 4 °C is suitable for short-term maintenance, 25-28 °C for routine functional assays, and 37 °C should be avoided. These findings provide valuable insights into the stress responses of protoplasts and establish a foundation for future research aimed at improving plant stress tolerance through protoplast-based techniques.

Zea mays↗

PubMed2026

Oxidative stress and cancer: current insights and therapeutic implications.

OXIDATIVE STRESS: good or evil? Oxidative stress occurs when the balance between reactive oxygen species (ROS) and antioxidant defenses shifts toward an excess of ROS; while essential in physiological processes, it plays a context-dependent role in cancer, contributing to both the promotion and inhibition of tumorigenesis. Small to moderate amounts of ROS activate pathways supporting tumor progression and proliferation, while large amounts lead to genomic instability and cell death. ROS are generated endogenously and exogenously. In cancer, ROS activate pathways that prompt tumor development (KRAS, MYC, PI3K-Akt-mTOR) and block tumor suppressors (p53, BRCA1), allowing tumorigenesis and drug resistance. They also modulate the tumor microenvironment (TME) by altering tumor, stromal and immune cell interactions, which initiate angiogenesis, epithelial-mesenchymal transition (EMT), inflammation and metastasis. Myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) contribute to ROS-driven immunosuppression. Cancer cells mainly rely on glycolysis and oxidative phosphorylation (OXPHOS) to sustain their energetic and metabolic requirements. Generated ROS act as metabolic byproducts and signaling molecules supporting proliferation and tumorigenesis. Cancer stem cells (CSCs) produce low ROS levels by activating antioxidant pathways and mitochondria remodeling, ensuring recurrence and persistence. There is a redox duality that presents challenges and opportunities for therapies. Pro-oxidant approaches attempt to overwhelm the tumor's defenses, while antioxidants preserve healthy tissues. Advances in targeted redox modulation with immunotherapies improve therapy effectiveness. We propose a new "Adaptive Directed Redox Therapy" (ADRT), which involves a dynamic, feedback-controlled methodology that alternates pro- and antioxidant phases to selectively collapse tumor redox balance while preserving normal tissues.

Humans↗

PubMed2026

The dirigent protein MsDIR6 functions in drought tolerance and modulates reactive oxygen species scavenging and secondary metabolite biosynthesis in alfalfa.

Alfalfa (Medicago sativa L.) is a globally significant forage crop essential for ensuring global food security. However, soil water deficit leads to a substantial decline in its yield, posing a severe threat to sustainable forage production. Dirigent (DIR) proteins play important roles in lignan biosynthesis and plant stress responses. Here, we identified 52 MsDIR genes in alfalfa through a genome-wide analysis, and screened MsDIR6 as a key candidate gene associated with drought tolerance. The results of qRT-PCR showed that MsDIR6 transcription was significantly induced by drought stress in alfalfa. MsDIR6 was preferentially expressed in roots and leaves, and its protein was localized in the nucleus and plasma membrane. Heterologous expression of MsDIR6 in yeast improved tolerance to mannitol-triggered osmotic stress. Heterologous overexpression of MsDIR6 in Arabidopsis significantly increased seed germination rate, seedling survival rate, and antioxidant capacity under drought stress, while improving leaf water-holding capacity by regulating stomatal movement. In transgenic alfalfa hairy roots, MsDIR6 alleviated drought-induced growth inhibition and enhanced reactive oxygen species (ROS) scavenging mediated by the antioxidant defense system under drought stress. Transcriptomic analysis revealed that MsDIR6 activated key genes in the phenylpropanoid and flavonoid biosynthesis pathways, which are crucial for ROS scavenging during drought adaptation. Additionally, we observed elevated flavonoid and lignin contents in MsDIR6-overexpressing alfalfa. Collectively, our findings offer novel insights into alfalfa's drought tolerance mechanisms and identify MsDIR6 as a promising genetic resource for molecular breeding strategies to improve this vital forage crop.

Alfalfa↗

PubMed2025

Fe-S cluster deficiency drives small colony variant formation in persistent infections.

INTRODUCTION: Small colony variants (SCVs) of Staphylococcus aureus (S. aureus) are associated with persistent infections and poor clinical outcomes. The mechanisms driving stable SCV formation remain poorly understood, particularly concerning metabolic adaptations. This study explores the in-host evolutionary dynamics of S. aureus and identifies a novel genetic determinant linked to SCV formation. OBJECTIVES: To investigate the genetic mutations and phenotypic adaptations underlying SCV formation, with a focus on the role of a novel mutation in the sufB gene, which is critical for Fe-S cluster biosynthesis. METHODS: Sequential isolates from a patient with recurrent infections were analyzed using whole-genome sequencing, antimicrobial susceptibility testing, and functional assays. The phylogenetic relationship of the isolates was determined, and specific mutations were identified. Functional assays included aconitase and glutamate synthase activity measurements, ATP level quantification, reactive oxygen species (ROS) production, and biofilm formation assays. In vivo pathogenesis was assessed using a murine catheter infection model. RESULTS: A novel frameshift mutation in sufB was identified, disrupting Fe-S cluster biosynthesis and impairing the TCA cycle and electron transport chain, leading to reduced ATP and ROS production. This metabolic reprogramming promoted stable SCV formation, characterized by slow growth, enhanced tolerance to antibiotics and neutrophil-mediated killing, and persistent inflammation in vivo. Restoration of sufB reversed these phenotypes, confirming its pivotal role in SCV-associated persistence. CONCLUSION: sufB is a novel genetic determinant of stable SCV formation through Fe-S cluster deficiency, driving metabolic shifts that enhance immune evasion and chronic infection. Our findings highlight antibiotic stewardship and suggest potential therapeutic strategies for managing persistent SCV-associated infections.

Staphylococcus aureus↗

PubMed2026

Beyond NAD Depletion: SARM1-Induced ATP Collapse Involves Direct ATP Degradation and Mitochondrial Dysfunction and Is Pharmacologically Reversible.

Sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 (SARM1) is an inducible NAD-consuming enzyme and execution factor in axon degeneration. Rapid ATP collapse after SARM1 activation, however, is not fully explained by NAD depletion alone. We used SARM1-overexpressing HEK293 cells and the cell-permeant activator CZ-48 to examine SARM1-induced non-apoptotic cell death, termed sarmoptosis. CZ-48 induced cell death that was suppressed by HSP90/70-annotated ATP-competitive compounds, especially geldanamycin and VER-155008 (VER), without reducing SARM1 abundance. VER preserved NAD and ATP during SARM1 activation but failed to rescue FK866-mediated NAD starvation, thereby distinguishing CZ-48/SARM1-driven cytotoxicity from generic NAD depletion. In cell-free assays, purified SARM1 reduced ATP levels; this effect was enhanced by SARM1's activator NMN and attenuated by its pharmacological inhibitors, although the in vitro activity was modest and the reaction products remain to be identified. ATPase-related perturbations, including thapsigargin and bafilomycin A1, also protected cells from CZ-48-induced death, further supporting a central role for ATP collapse in sarmoptosis. iTRAQ proteomics, MitoSOX Red staining, and DiOC6(3) staining revealed that CZ-48 treatment was associated with mitochondrial and metabolic remodeling, mitochondrial ROS accumulation, and mitochondrial depolarization, all of which were mitigated by VER. Collectively, these findings support a convergent ATP-collapse model in which SARM1 activation promotes NAD depletion, directly consumes ATP, and is associated with mitochondrial dysfunction that may amplify ATP-production failure.

ATP collapse↗

PubMed2025

Multi-Omics Platforms Reveal Synergistic Intestinal Toxicity in Tilapia from Acute Co-Exposure to Polystyrene Microplastics, Sulfamethoxazole, and BDE153.

Polystyrene microplastic (MP) and its co-existing contaminants may exert different toxic effects on its surrounding aquatic organisms. In order to detect the intestinal harmful responses, tilapia were subjected to exposure with 75 nm of MPs, 100 ng·L-1 of sulfamethoxazole (SMZ), 5 ng·L-1 of BDE153, and combinations thereof over periods of 2, 4, and 8 days. Enzymatic assays, transcriptomics, proteomics, and metabolomics were employed to evaluate intestinal histopathological effects. Results showed that significant reductions were observed in ATP, ROS, SOD, EROD, lipid metabolism-related enzymes, pro-inflammatory cytokines (TNFα and IL-1β), and apoptosis marker caspase 3 across all groups at day 8. Histological evaluation revealed diminished goblet cell density, with distinct vacuole formation in the BDE153+MPs group. KEGG pathway analysis highlighted disruptions in endocytosis, MAPK signaling, phagosome formation, and actin cytoskeleton regulation. Proteomic findings indicated notable enrichment in endocytosis (decreased sorting nexin-2; increased Si:dkey-13a21.4), MAPK/PPAR signaling, protein processing in the endoplasmic reticulum (Sec61 subunit gamma), and cytoskeletal modulation (reduced fibronectin; elevated activation peptide fragment 1), with or without SMZ and BDE153. Metabolomic profiling showed significant alterations in ABC transporters, aminoacyl-tRNA biosynthesis, protein digestion and absorption, and linoleic acid metabolism. In summary, these findings suggest that BDE153 and MPs synergistically exacerbate intestinal damage and gene/protein expression over time, while SMZ appears to exert an antagonistic, mitigating effect.

Animals↗

PubMed2016

Tracer-Based Metabolic NMR-Based Flux Analysis in a Leukaemia Cell Line.

High levels of reactive oxygen species (ROS) have a profound impact on acute myeloid leukaemia cells and can be used to specifically target these cells with novel therapies. We have previously shown how the combination of two redeployed drugs, the contraceptive steroid medroxyprogesterone and the lipid-regulating drug bezafibrate exert anti-leukaemic effects by producing ROS. Here we report a 13C-tracer-based NMR metabolic study to understand how these drugs work in K562 leukaemia cells. Our study shows that [1,2-13C]glucose is incorporated into ribose sugars, indicating activity in oxidative and non-oxidative pentose phosphate pathways alongside lactate production. There is little label incorporation into the tricarboxylic acid cycle from glucose, but much greater incorporation arises from the use of [3-13C]glutamine. The combined medroxyprogesterone and bezafibrate treatment decreases label incorporation from both glucose and glutamine into α-ketoglutarate and increased that for succinate, which is consistent with ROS-mediated conversion of α-ketoglutarate to succinate. Most interestingly, this combined treatment drastically reduced the production of several pyrimidine synthesis intermediates.

NMR spectroscopy↗

PubMed2026

CD4+T cell metabolic reprogramming as therapeutic targets in neurodegenerative diseases.

Neurodegenerative diseases are a group of disorders characterized by the progressive loss of structure and function of neurons in the brain and/or peripheral nervous system. The main pathological feature of neurodegenerative disease in the central nervous system (CNS) is the selective neuronal loss in the brain and spinal cord, leading to cognitive and/or motor dysfunction. The immune system plays a variety of roles in the pathophysiology of neurodegenerative diseases. CD4+T cells are being recognized as important immunometabolic modulators in the pathophysiology of neurodegenerative disorders (ND), including multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD). Their varied metabolic patterns provide a special therapeutic window for regulating neuroinflammation, spanning from lipid-dependent regulatory T cells (Tregs) to glycolysis-driven pro-inflammatory subsets (Th1, Th17). Abnormal immune metabolism raises the risk of oxidative stress, mitochondrial malfunction, and neuronal death in neurodegenerative environments. According to recent research, altering CD4 T cell metabolism to favour oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) may help Treg function return and inhibit harmful effector responses. Current research on CD4 T cell immunometabolic pathways, their interactions with CNS-resident cells, and the developing possibility of metabolic intervention to slow neurodegeneration is explained in this review. By examining important signaling pathways including AMPK, mTORC1, and ROS dynamics, we demonstrate how CD4+T cell metabolism may reshape ND treatment approaches.

Humans↗

PubMed2025

Insights into salt adaptation from comparative genomics of Scirpus mariqueter and a related freshwater species.

The evolutionary mechanisms underlying ecological divergence between closely related species remain a central question in biology. Scirpus mariqueter is a coastal halophyte thriving in the saline intertidal zone and exhibits marked adaptive differences compared to its freshwater relative Bolboschoenus planiculmis. However, the genomic and physiological bases of its salt tolerance remain poorly understood. We generated high-quality genome assemblies for both species and investigated the anatomical and physiological innovations underpinning S. mariqueter's adaptation to extreme environments. Morphological analyses revealed that S. mariqueter evolved specialized traits-including denser leaf palisade tissues, enhanced stem aerenchyma, and compact root cortices-synergistically limiting salt intrusion. Using chromosome-level genomes, we identified lineage-specific expansions in S. mariqueter of gene families critical for salinity tolerance, including those regulating carbohydrate metabolism, photosynthetic fidelity, and reactive oxygen species (ROS) detoxification. Strikingly, germin-like protein (GLP) and wound-induced protein (WIP) families contain tandem repeats mediating ROS scavenging and cell wall integrity, underwent adaptive expansion, paralleling anatomical innovations. Physiological profiling under salt stress confirmed S. mariqueter's unique capacity to maintain photosynthetic activity and carbohydrate production, directly linking genomic adaptations to functional resilience. This study reveals an adaptive strategy whereby structural modifications, diversification of stress-responsive gene families, and metabolic stability collectively enable S. mariqueter to thrive in saline ecosystems.

Salt Tolerance↗

PubMed2025

Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling.

PURPOSE: Type I interferonopathy encompasses disorders marked by systemic inflammation and neurological involvement, arising from genetic mutations that result in the upregulation of type I IFN signaling through various mechanisms. Currently, therapeutic options are limited, and no standard therapy exists. This study aims to develop a strategy for identifying new therapeutic targets for type I interferonopathy using induced pluripotent stem cells (iPSCs). METHODS: The IFIH1 R779H variant was introduced into iPSCs through genome editing. RNA sequencing of iPSC-derived dendritic cells (DCs) was performed, and differentially expressed genes (DEGs) were identified. IFN-α secretion, reactive oxygen species (ROS), and mitochondrial oxygen consumption rate (OCR) were analyzed in iPSC-derived DCs. An in silico prediction of compounds binding to the OAS-like domain was conducted. Candidate compounds were evaluated for their ability to inhibit IFN secretion from IFIH1 R779H-mutated iPSC-derived DCs. RESULTS: Transcriptome analysis indicated upregulation of the IFN-related and metabolic pathways. IFIH1 R779H-mutated iPSC-derived DCs exhibited increased OCR and ROS generation, and blocking mitochondrial metabolism significantly reduced excessive IFN-α secretion. Among the DEGs, PML was upregulated, and targeting this gene with arsenic trioxide (ATO), a PML antagonist, suppressed IFN-α secretion from IFIH1 R779H-mutated iPSC-derived DCs. Additionally, bisantrene, phthalylsulfathiazole and ganaplacide were predicted to bind to the RNA binding groove of OAS-like domain of human OASL in silico, effectively inhibiting IFN-α secretion from IFIH1 R779H-mutated DCs. CONCLUSION: Our iPSC-based disease modeling and drug investigation approach provides a robust platform for validating the efficacy and toxicity of candidate therapeutic agents for rare and intractable human diseases such as type I interferonopathy.

Humans↗

PubMed2025

Interaction and regulation of the mitochondrial proteome - in health and disease.

INTRODUCTION: Mitochondria contain multiple pathways including energy metabolism and several signaling and synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases including inherited metabolic disorders, complex and common disorders like neurodegeneration, diabetes, and cancer, since they all to some degree have mitochondrial underpinnings. AREAS COVERED: The main mitochondrial functions and pathways are outlined, and systematic protein lists are presented. The main energy metabolic pathways are as follows: iron-sulfur cluster synthesis, one carbon metabolism, catabolism of hydrogen sulfide, kynurenines and reactive oxygen species (ROS), and others, described with the aim of laying a foundation for systematic mitochondrial pathway analysis based on proteomics data. The links of the proteins and pathways to functional effects and diseases are discussed. The disease examples are focussed on inherited metabolic disorders, cancer, neurological, and cardiovascular disorders. EXPERT OPINION: To elucidate the role of mitochondria in health and disease, there is a need for comprehensive proteomics analyses with stringent, systematic data treatment for proper interpretation of mitochondrial pathway data. In that way, comprehensive hypothesis-based research can be performed based on proteomics data.

Humans↗

PubMed2026

Impact of oxidative stress on malignant tumor progression and emerging therapeutic strategies.

Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cancer biology. While persistent, moderately elevated ROS levels can promote genomic instability, tumor progression, and immune evasion, excessive ROS accumulation can overwhelm antioxidant defenses and trigger cancer cell death. Despite promising preclinical findings, clinical translation remains a challenge because of the context-dependent effects of ROS. A deeper understanding of oxidative stress regulation may lead to the development of novel precision medicine strategies, optimizing cancer therapies while minimizing adverse effects. This review highlights the concentration-dependent effects of oxidative stress in tumorigenesis, focusing on its impact on DNA damage, metabolic reprogramming, and immune modulation. We discuss recent advancements in ROS-targeting strategies, including pro-oxidant therapies that exploit redox vulnerabilities in cancer cells and antioxidant-based approaches aimed at mitigating oxidative stress-driven resistance to treatment. Moreover, we examine the interplay between oxidative stress and the tumor microen-vironment, emphasizing its influence on immune surveillance and therapeutic responses. This re-view provides insights into ROS-targeting interventions and their potential in oncologic treatment paradigms.

malignant tumors↗

PubMed2026

AKR7A3 rs1738023 association with susceptibility to female hepatocellular carcinoma and its role in AFB1 metabolism and tumor.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancer worldwide. In this study, we performed a two-stage exome-chip association analysis and found that the aldo-keto reductase family7 member A3 (AKR7A3) rs1738023 may be a potential susceptibility locus for HCC in females. We aimed to explore its role and mechanism. METHODS: The association between genotype and phenotype was analyzed through GWAS method. The expression of AKR7A3 in cancer tissue and blood analysis by qRT-PCR. The relationship of AKR7A3 and aflatoxin B1 (AFB1) was also analyzed. The effect of AKR7A3 on the biological behavior of HCC cell line was investigated on proliferation and invasion. The potential mechanism was analyzed by transcriptome analysis and western blot. RESULTS: Through genome-wide association analysis (GWAS), AKR7A3 (rs1738023), KIF2C (rs4342887), and CYP3A5 (rs6977165 and rs4646450) were found to be associated with susceptibility to hepatocellular carcinoma (HCC) in women. Further expression quantitative trait loci (eQTL) analysis showed that only AKR7A3 (rs1738023) was significantly associated with gene expression. The expression of AKR7A3 was significantly lower in HCC than adjacent non-tumorous tissues (P < 0.001). The genotype of rs1738023 was significantly associated with AKR7A3 expression (P = 0.0085). Rs1738023[C] genotype had a low AKR7A3 expression level and limited detoxification ability of AFB1. Literature data showed that AKR7A3 is involved in the metabolism of aflatoxin B1 (AFB1). Functional experimental results showed that overexpression of AKR7A3 in the normal liver cell line HL-7702 could significantly reduce AFB1-induced ROS levels and DNA adduct formation, suggesting that it plays a protective role in AFB1 metabolic detoxification. Cell function test showed that overexpression of AKR7A3 inhibit the proliferation, migration and invasion of HCC cells, and block the cell cycle. Transcriptome sequencing and KEGG pathway enrichment analysis revealed that overexpression of AKR7A3 affected the PI3K signaling pathway and led to downregulation of HIF1A and its downstream VEGFA protein expression. The validation results were confirmed in HCC cell lines Huh-7 and SUN-387. CONCLUSION: Overexpression of AKR7A3 contributes to inhibition of HCC progression and reduction of aflatoxin toxicity. AKR7A3 may serve as a potential prognostic and therapeutic target for HCC patients, although further validation is needed.

AKR7A3↗

PubMed2026

Influence of microplastics on microalgal performance during wastewater polishing.

Microplastics (MPs) are emerging contaminants that are increasingly accumulating in aquatic ecosystems due to excessive anthropogenic activity and insufficient mitigation strategies, posing serious environmental and public health risks. Their impact on wastewater (WW) treatment processes remains poorly understood. This study evaluated the effects of five MPs commonly found in WW - polypropylene, polystyrene, polyamide, low-density polyethylene, and high-density polyethylene - on the physiology and bioremediation performance of the microalga Chlorella vulgaris in synthetic WW (SWW). Metabolic responses were assessed via esterase activity and intracellular reactive oxygen species (ROS), while nitrogen (N), phosphorus (P), and glucose removal were monitored to evaluate bioremediation efficiency. MPs inhibited esterase activity and elevated ROS levels, indicating oxidative stress. Nevertheless, C. vulgaris maintained a high bioremediation capacity (> 75 % N, > 60 % P, and > 70 % for glucose). Environmental conditions modulated microalga response to MPs exposure. Under N-limited conditions, C. vulgaris exhibited enhanced nutrient uptake and biomass production, but a 12 h/12 h light/dark photoperiod reduced N removal but stimulated glucose consumption via heterotrophic metabolism. In contrast, C-limited conditions exacerbated oxidative stress and compromised nutrient removal, resulting in residual concentrations exceeding legal limits. These findings highlight that environmental factors can either mitigate or exacerbate the physiological stress induced by MPs, ultimately affecting WW polishing. This work provides a comprehensive insight into the cellular and metabolic effects of MPs on microalgae and supports C. vulgaris as a resilient and sustainable approach for nutrient and carbon removal in MP-contaminated WW systems.

Microalgae↗

PubMed2024

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr increased both respiration and fermentation but decreased ATP levels and growth, suggesting that Δagr cells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived "memory" of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

Staphylococcus aureus↗

PubMed2024

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Cybb-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

Staphylococcus aureus↗

PubMed2025

The SlWRKY39-SlZF61 module synergistically regulates SlGSTU42 to enhance low-temperature tolerance in tomato.

Low-temperature stress affects plant growth, and WRKY transcription factors alleviate such damage by regulating downstream genes. This study found that tomato SlWRKY39 significantly responds to low temperatures: its overexpression enhances seedling low-temperature tolerance by promoting ROS scavenging, while knockout exacerbates ROS accumulation and increases sensitivity to low temperatures. Transcriptome analysis indicated induction of glutathione metabolic pathway genes in slwrky39 plants under low-temperature stress. Y1H, EMSA, and Dual-LUC experiments confirmed that SlWRKY39 specifically binds to and activates the SlGSTU42 promoter; silencing SlGSTU42 attenuated the low-temperature tolerance conferred by SlWRKY39 overexpression, verifying that SlWRKY39 improves low-temperature tolerance via direct regulation of SlGSTU42. Additionally, SlZF61 interacts with SlWRKY39, enhancing its regulatory effect on SlGSTU42. SlZF61 overexpression strengthens low-temperature tolerance, while knockout increases sensitivity to low temperatures. In summary, under low-temperature stress, SlWRKY39 and SlZF61 are upregulated expression in tomato; SlWRKY39 binds to the SlGSTU42 promoter, and SlZF61 interacts with SlWRKY39 to form a protein complex, enhancing this binding. They synergistically activate SlGSTU42 transcription, thereby improving seedling low-temperature tolerance by scavenging ROS. This coordinated regulatory mechanism provides a new theoretical basis and practical insights for enhancing tomato low-temperature tolerance and ensuring stable production under low-temperature stress conditions.

Solanum lycopersicum↗

PubMed2026

Plasticity of hepatic metabolism in Arctic char (Salvelinus alpinus) in response to cyclic hypoxia.

The emergence of cyclic hypoxia puts aquatic organisms' homeostasis under significant strain. Energetic metabolism as well as protein synthesis and folding are particularly altered during hypoxia, while reoxygenation imposes an oxidative challenge. Currently, little is known about how hypoxia-sensitive organisms respond to large oxygen fluctuations. Our previous work on Arctic char revealed that this salmonid, despite being strongly affected by acute hypoxia and reoxygenation (H/R), can successfully reestablish homeostasis, notably through adjustments to hepatic mitochondrial metabolism. However, the mechanisms underlying this acclimation remain poorly understood. We hypothesized that Arctic char remodel their hepatic proteome to optimize energy metabolism, reorganize oxygen-demanding pathways, and maintain cellular homeostasis during repeated H/R cycles. By exposing Arctic char to two or fifteen days of diel cyclic hypoxia, we confirmed this species' limited capacity to respond to acute H/R. Nevertheless, after fifteen cycles, fish adjusted their energetic metabolism through coordinated regulation of carbohydrate and lipid pathways and upregulation of amino acid metabolism. Mitochondrial metabolism was strongly reorganized, particularly at the ubiquinone-Complex III interaction level, alongside adjustments in proline utilization and protein processing. Moreover, protein processing and folding pathways were stimulated in both mitochondria and the endoplasmic reticulum. However, chronic cyclic hypoxia may still promote non-mitochondrial ROS production, DNA replication stress, and impaired immune function. This study highlights how a hypoxia-sensitive fish progressively reorganizes its metabolism and oxygen-demanding pathways to establish a phenotype adapted to chronic cyclic hypoxia, while also revealing the physiological costs associated with this acclimation.

Animals↗