Redox Biology最新文献

{"title":"Carbon ion combined photon radiotherapy induces ferroptosis via NCOA4-mediated ferritinophagy in glioblastoma","authors":"Li Chen ,&nbsp;Wanzun Lin ,&nbsp;Ziyu Le ,&nbsp;Fangzhu Wan ,&nbsp;Haojiong Zhang ,&nbsp;Shikai Geng ,&nbsp;Qingting Huang ,&nbsp;Jing Gao ,&nbsp;Wei Hu ,&nbsp;Huaiyuan Chen ,&nbsp;Xingyu Liu ,&nbsp;Chunlin Shao ,&nbsp;Fengtao Su ,&nbsp;Jiade J. Lu ,&nbsp;Lin Kong","doi":"10.1016/j.redox.2025.103865","DOIUrl":"10.1016/j.redox.2025.103865","url":null,"abstract":"<div><div>Glioblastoma (GBM), the most prevalent and lethal primary malignancy of the central nervous system, remains refractory to conventional photon radiotherapy due to inherent limitations in dose distribution. Although carbon ion radiotherapy offers distinct advantages, including its characteristic Bragg peak deposition and superior relative biological effectiveness, its clinical application is constrained by high costs and increased toxicity. This study explores the radiobiological interactions underlying a mixed carbon ion-photon irradiation regimen, a promising strategy in advanced particle therapy. Our findings demonstrate that combined irradiation exerts synergistic cytotoxic effects in GBM models. Mechanistic analysis reveals that this combination induces clustered DNA double-strand breaks, leading to the cytoplasmic accumulation of double-stranded DNA (dsDNA) fragments. This, in turn, activates the cGAS-STING-mediated cytosolic DNA sensing pathway, which facilitates NCOA4-FTH1 axis-driven ferritinophagy and ultimately triggering iron-dependent ferroptosis. These findings offer a new mechanistic perspective on optimizing combined particle therapy regimens for GBM treatment, with significant implications for translational applications in clinical radiation oncology.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103865"},"PeriodicalIF":11.9,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to an environmentally relevant mixture of polychlorinated biphenyls affects mitochondrial bioenergetics and plasticity","authors":"Maria Carolina Peixoto-Rodrigues ,&nbsp;Vladimir Pedro Peralva Borges-Martins ,&nbsp;José Raphael Monteiro-Neto ,&nbsp;Bruno Vicente ,&nbsp;Lucas José Guimarães ,&nbsp;Clara Fernandes-Carvalho ,&nbsp;Antonio Galina ,&nbsp;Victor Midlej ,&nbsp;Michal Toborek ,&nbsp;Rachel Ann Hauser-Davis ,&nbsp;Daniel Adesse","doi":"10.1016/j.redox.2025.103862","DOIUrl":"10.1016/j.redox.2025.103862","url":null,"abstract":"<div><div>Adaptations of cells to environmental insults typically require tightly regulated processes to preserve the organismal steady state, particularly in metabolically active cells such as neural cells. Polychlorinated biphenyls (PCBs) are persistent organic pollutants widely recognized for their neurotoxic potential. Due to their lipophilic nature, these compounds readily accumulate in the brain, where they can disrupt neuronal homeostasis. Herein, we examined the effects of exposure to an environmentally relevant PCB mixture on mitochondrial dynamics, ultrastructure, and function in the mouse neuroblastoma Neuro2a cell line. Ultrastructural examinations indicated evident signs of mitochondrial damage, including swelling, cristae disruption, and increased frequency of autophagic structures. Quantification of mitochondrial networks confirmed a shift from tubular to fragmented morphologies, accompanied with the modulation of the gene expression of genes involved in mitochondrial fusion and fission. Specifically, mitofusin 2 protein levels were increased at 24 and 48 h of treatment, and OPA1 at 48 h, whereas Drp1, phosphorylated at Ser616 was increased at 24 h. Markers of mitophagy PINK1 and Parkin were elevated at 72 and 48 h of exposure, respectively, whereas Atg5 and Atg7, markers of autophagy were increased at 24 h. We observed a decrease in mitochondrial membrane potential and increase in mtDNA levels in PCB-treated cultures at 24 h. Oxidative stress was also implicated by overexpression and increased enzymatic activity of superoxide dismutase 1 (SOD1). Functional tests revealed a transient impairment of mitochondrial respiration and ATP synthesis, which was later restored, pointing to the recruitment of compensatory mechanisms. Together, these results indicate that PCB exposure activates an integrated stress response with oxidative imbalance, mitochondrial bioenergetics, remodeling, and autophagy features, revealing the neural cell vulnerability and plasticity to environmental insult.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103862"},"PeriodicalIF":11.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoskeletal disruption-induced calcium dysregulation drives cell death in anti-IgLON5 disease","authors":"Lisanne Korn ,&nbsp;Júlia Csatári ,&nbsp;Andreas Schulte-Mecklenbeck ,&nbsp;Laura Vinnenberg ,&nbsp;Nadine Ritter ,&nbsp;Paul Disse ,&nbsp;Isabel Aymanns ,&nbsp;Jan D. Lünemann ,&nbsp;Catharina C. Gross ,&nbsp;Petra Hundehege ,&nbsp;Guiscard Seebohm ,&nbsp;Heinz Wiendl ,&nbsp;Thilo Kaehne ,&nbsp;Matthias Pawlowski ,&nbsp;Stjepana Kovac","doi":"10.1016/j.redox.2025.103854","DOIUrl":"10.1016/j.redox.2025.103854","url":null,"abstract":"<div><div>Anti-IgLON5 disease is an autoimmune encephalitis with more chronic presentation including memory decline, sleep disorder, bulbar symptoms and movement disorder. Post-mortem brains of patients with anti-IgLON5 disease show neurodegeneration with tau deposition sparking interest in this ‘acquired tauopathy’ as a disease model for neurodegeneration, yet mechanisms of neurodegeneration remain unknown. Using a reductionist human iPSC-derived neuron-antibody model, we applied proteomics approach, electrophysiology and live cell imaging. iNeurons treated with anti-IgLON5 IgG presented with cytoskeletal disruption along with tau depositions, which correlated with endophenotypes. Accompanying calcium dysregulation was driven by impaired ER refill and mitochondrial dysfunction leading to cell death. Analogous cytoskeletal disruption is also reflected in the serum of treatment naïve patients using OLink proteomics. These findings provide insight into anti-IgLON5 disease pathology and pinpoint downstream signalling events of direct antibody-neuron interactions, which involve novel targets such as cytoskeletal disruption along with calcium dysregulation.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103854"},"PeriodicalIF":11.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thioredoxin-interacting protein as a crucial regulator in asthma exacerbation induced by copper oxide nanoparticles in a mouse model","authors":"Woong-Il Kim ,&nbsp;So-Won Pak ,&nbsp;Sin-Hyang Park ,&nbsp;Ba-Reun Jin ,&nbsp;Junhyeong Lee ,&nbsp;Min-Jung Park ,&nbsp;Changjong Moon ,&nbsp;Won-Kee Yoon ,&nbsp;Sung-Hwan Kim ,&nbsp;In-Sik Shin ,&nbsp;Jong-Choon Kim","doi":"10.1016/j.redox.2025.103863","DOIUrl":"10.1016/j.redox.2025.103863","url":null,"abstract":"<div><div>Copper oxide nanoparticles (CuONPs) are increasingly used across various industrial applications, raising concerns about their potential toxicity and necessitating comprehensive safety evaluations. In this study, we first evaluated the respiratory toxicity of CuONP exposure in a mouse model of asthma. CuONP exposure alone exacerbated asthma symptoms, as evidenced by increased airway hyperresponsiveness, inflammatory cell infiltration, and elevated cytokine production with increasing thioredoxin-interacting protein (TXNIP) expression. We then investigated whether TXNIP functions as a critical regulator of asthma exacerbation by examining the effects of TXNIP on the same experimental models using induced TXNIP-overexpressed mice induced by intratracheal injection of adeno-associated virus (AAV)2/8 and TXNIP knock-out (KO) mice. In CuONP-exposed asthmatic animals, TXNIP overexpressed animals significantly increased airway hyperresponsiveness, inflammatory cell counts and the production of helper type 2 cytokines, including interleukin (IL)-5 and IL-13, as well as the IL-1β, IL-6, tumor necrosis factor (TNF)-α, interferon gamma (IFN-γ) and IL-10 compared with the green fluorescent protein (GFP)-expressing controls. These responses were accompanied by the elevation of inflammatory infiltration, mucus production and the expression of apoptotic markers in lung tissues. By contrast, TXNIP KO animals markedly reduced the pathophysiological factors, inflammatory responses, mucus production and the expression of apoptotic markers in lung tissue compared with the wild-type (WT) animals. Collectively, these findings demonstrate that TXNIP plays a crucial role in regulating inflammatory responses and cell death in CuONP-exposed asthmatic mice, suggesting its potential as a therapeutic target for CuONP-induced asthma exacerbation.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103863"},"PeriodicalIF":11.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond","authors":"Nada Ahmed Selim ,&nbsp;Andrew P. Wojtovich","doi":"10.1016/j.redox.2025.103859","DOIUrl":"10.1016/j.redox.2025.103859","url":null,"abstract":"<div><div>Mitochondria are central to cellular function, acting as metabolic hubs that regulate energy transduction to communicate cellular status. A key component of this energetic regulation is the mitochondrial membrane potential (MMP), a charge separation across the inner mitochondrial membrane generated by the electron transport chain. Beyond MMP's canonical role in driving ATP synthesis, MMP acts as a dynamic signaling hub. MMP rapidly adjusts to acute changes in cellular energy demand and undergoes sustained modifications during developmental processes, such as neuronal remodeling. Changes in MMP influence reactive oxygen species (ROS) production, calcium handling, and mitochondrial quality control, enabling localized and time-sensitive regulation of cellular function. In neurons, changes in MMP coordinate synaptic plasticity by linking metabolic state to structural changes at synapses. This review highlights the non-canonical roles of MMP in signal integration, spatial organization, and stress adaptation, providing a broader framework for understanding mitochondrial contributions to health and disease.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103859"},"PeriodicalIF":11.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small extracellular vesicles orchestrated pathological communications between breast cancer cells and cardiomyocytes as a novel mechanism exacerbating anthracycline cardiotoxicity by fueling ferroptosis","authors":"Dong Han ,&nbsp;Tianhu Wang ,&nbsp;Xiaoyao Li ,&nbsp;Cheng Qin ,&nbsp;Yingjie Zhang ,&nbsp;Tingwen Zhou ,&nbsp;Shan Gao ,&nbsp;Weiwei Zhang ,&nbsp;Yongjun Wang ,&nbsp;Yan Ma ,&nbsp;Feng Cao","doi":"10.1016/j.redox.2025.103843","DOIUrl":"10.1016/j.redox.2025.103843","url":null,"abstract":"<div><div>Small extracellular vesicles (sEVs) critically orchestrate inter-tissue and inter-organ communications and may play essential roles in heart-tumor interaction. However, whether cancer-secreted sEVs affect the progression of doxorubicin-induced cardiotoxicity (DOXIC) <em>via</em> orchestrating the tumor cell-cardiomyocyte crosstalk has not yet been explored. Herein, we reveal that Doxorubicin (DOX)-treated breast cancer cells secrete sEVs (D-BCC-sEVs) that exacerbate DOX-induced ferroptosis of human iPSC-derived cardiomyocytes (hiCMs). miRNA expression profiling and experimental validations reveal that miR-338-3p is upregulated in D-BCC-sEVs and mediate its detrimental effects. Incubation of hiCMs with D-BCC-sEVs or overexpression of miR-338-3p alone intensifies DOX-induced ferroptosis. N⁶-methyladenosine (m⁶A) is revealed to mediate the upregulation of miR-338-3p in D-BCCs. D-BCCs-enriched miR-338-3p is packaged in sEVs and transferred into hiCMs in a RBMX-dependent manner, miR-338-3p further targets anti-ferroptotic genes CP, SLC7A11, and GPX4 to facilitate their degradation. Therapeutically, dual-functional decoying sEVs encapsulated with miR-338-3p inhibitor mitigate DOXIC in an orthotopic breast cancer mouse model. Clinically, plasma sEVs isolated from patients experiencing DOXIC enhance DOX-induced ferroptosis in hiCM, which is rescued by miR-338-3p inhibitor. Our findings uncovered for the first time that DOX-treated BCCs exacerbated DOXIC through releasing pro-ferroptotic miR-338-3p-enriched sEVs. Therefore, targeting sEVs-mediated tumor/cardiomyocyte pathological communication may offer a novel approach for the management of DOXIC.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103843"},"PeriodicalIF":11.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1R activation restores Gas6-driven efferocytosis in senescent foamy macrophages to promote neural repair","authors":"Mingjie Xia ,&nbsp;Chaochen Li ,&nbsp;Yanan Zhang ,&nbsp;Tianyi Wang ,&nbsp;Chaoqiang Zhang ,&nbsp;Jian Zhou ,&nbsp;Xuexian Zhu ,&nbsp;Hongxiang Hong ,&nbsp;Haijun Li ,&nbsp;Zhanyang Qian ,&nbsp;Zhiming Cui","doi":"10.1016/j.redox.2025.103857","DOIUrl":"10.1016/j.redox.2025.103857","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a devastating condition characterized by the accumulation of myelin debris (MD), persistent neuroinflammation, and impaired neural regeneration. Although macrophages are pivotal for MD clearance, the impact of excessive MD phagocytosis on macrophage phenotype and function remains poorly understood. Building upon our prior evidence that exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, mitigates microglia-driven neuroinflammation post-SCI, this study elucidates the therapeutic efficacy and underlying mechanisms of Ex-4 in alleviating macrophage senescence, restoring efferocytotic capacity, and facilitating neural repair. Employing a T10 contusive SCI model in male C57BL/6 mice, <em>in vivo</em> administration of Ex-4 was combined with macrophage-specific knockdown of growth arrest-specific 6 (Gas6) via AAV-shRNA. Complementary <em>in vitro</em> assays involved bone marrow-derived macrophages (BMDMs) challenged with MD in the presence or absence of Ex-4 or AMP-activated protein kinase (AMPK) inhibition. Cellular senescence and efferocytosis were comprehensively assessed through live-cell imaging, immunofluorescence, senescence-associated β-galactosidase staining, quantitative PCR, and western blotting. Molecular docking and dynamics simulations elucidated GLP-1R–AMPK interactions, corroborated by <em>in vivo</em> validation. Results demonstrate that MD-engulfing macrophages exhibit foam cell-like morphology and upregulated senescence markers, including increased β-galactosidase activity and senescence-associated secretory phenotype, concomitant with diminished efferocytosis via downregulation of the Axl receptor. Senescent macrophages were shown to exacerbate neuronal apoptosis and astrocytic scar formation in co-culture systems. Ex-4 treatment significantly attenuated macrophage senescence, restored efferocytotic function, and reduced neuronal injury and astrocyte activation, effects contingent upon AMPK/Gas6/Axl pathway activation and abrogated by Gas6 knockdown. <em>In vivo</em>, Ex-4 administration enhanced remyelination, axonal regeneration, and functional recovery, while attenuating glial scar formation following SCI. Collectively, these findings identify macrophage senescence induced by excessive MD phagocytosis as a novel pathological contributor to SCI progression and establish Ex-4 as a promising therapeutic agent that restores macrophage homeostasis and promotes neural repair via GLP-1R/AMPK/Gas6/Axl signaling.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103857"},"PeriodicalIF":11.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring ferroptosis in vivo: Iron-driven volatile oxidized lipids as breath biomarkers","authors":"Yuta Matsuoka ,&nbsp;Yoshinori Katsumata ,&nbsp;Po-sung Chu ,&nbsp;Rei Morikawa ,&nbsp;Nobuhiro Nakamoto ,&nbsp;Kohta Iguchi ,&nbsp;Ken Takahashi ,&nbsp;Tadayuki Kou ,&nbsp;Ryo Ito ,&nbsp;Kojiro Taura ,&nbsp;Shujiro Yazumi ,&nbsp;Hiroaki Terajima ,&nbsp;Gen Honjo ,&nbsp;Genki Ichihara ,&nbsp;Yuki Muramoto ,&nbsp;Kazuki Sato ,&nbsp;Rae Maeda ,&nbsp;Kazuhiro Hata ,&nbsp;Naoya Toriu ,&nbsp;Motoko Yanagita ,&nbsp;Yuki Sugiura","doi":"10.1016/j.redox.2025.103858","DOIUrl":"10.1016/j.redox.2025.103858","url":null,"abstract":"<div><div>Ferroptosis, an iron-dependent cell death mechanism characterized by excessive lipid peroxidation, has been implicated in numerous human diseases and organ pathologies. However, current detection methods necessitate invasive tissue sampling to assess lipid peroxidation, making noninvasive detection of ferroptosis in human subjects extremely challenging. In this study, we employed oxidative volatolomics to comprehensively characterize the volatile oxidized lipids (VOLs) produced during ferroptosis. Polyunsaturated fatty acid-derived VOLs were generated via iron-dependent LPO and released extracellularly as ferroptosis progressed. These VOLs were specifically generated during hepatic ferroptosis in mouse models of acetaminophen-induced liver injury and metabolic dysfunction-associated steatohepatitis (MASH) and were also detectable in the exhaled breath of patients with MASH. Specific VOLs released upon iron-dependent LPO are potential markers of ferroptosis <em>in vivo</em> and may facilitate noninvasive monitoring of cellular health in humans.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103858"},"PeriodicalIF":11.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tectorigenin attenuates cardiac hypertrophy via USP9X/MCL1-mediated mitochondrial stabilization","authors":"Xiaoqiang Chen ,&nbsp;Genqing Zhou ,&nbsp;Tianyou Yuan ,&nbsp;Zongbin He ,&nbsp;Liuhang Su ,&nbsp;Huijiao Guo ,&nbsp;Fasheng Liang ,&nbsp;Lidong Cai ,&nbsp;Suiji Li ,&nbsp;Wenyi Yang","doi":"10.1016/j.redox.2025.103855","DOIUrl":"10.1016/j.redox.2025.103855","url":null,"abstract":"<div><div>Pathological cardiac hypertrophy, driven by mitochondrial dysfunction and maladaptive remodeling, remains a therapeutic challenge. This study explores the cardioprotective properties of tectorigenin (Tec) in the context of transverse aortic constriction (TAC)-induced hypertrophy, focusing on mitochondrial homeostasis. In animal models, administration of Tec improved survival rates, reduced cardiac dysfunction, and decreased hypertrophy and fibrosis in TAC mice, while preserving mitochondrial function. In <em>in vitro</em> experiments, Tec was found to inhibit the enlargement of cardiomyocytes and mitochondrial impairment induced by phenylephrine. The underlying mechanism revealed that Tec stabilizes MCL1, a key regulator of mitochondrial integrity, by promoting its deubiquitination through USP9X, thus preventing its degradation without relying on the PI3K-AKT signaling pathway. Notably, silencing either MCL1 or USP9X negated the anti-hypertrophic and antioxidant effects of Tec, underscoring their critical roles in this process. These findings position Tec as a novel modulator of the USP9X-MCL1-mitochondria axis, suggesting a new therapeutic approach to separate pathological remodeling from mitochondrial dysfunction in cardiac hypertrophy. By circumventing traditional survival pathways, Tec represents a mitochondria-focused strategy to slow the progression of heart failure, linking the pharmacology of natural compounds with the resilience of targeted organelles.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103855"},"PeriodicalIF":11.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidatively damaged DNA in DNA repair-deficient and ethanol-exposed fetal brains induces gene dysregulation and mitochondrial dysfunction associated with neurodevelopmental disorders","authors":"Ashley P. Cheng ,&nbsp;Piriththiv Dhavarasa ,&nbsp;Jana van Heeswyk ,&nbsp;Sophia M. Richards ,&nbsp;Xuan Li ,&nbsp;Aaron M. Shapiro ,&nbsp;Peter G. Wells","doi":"10.1016/j.redox.2025.103856","DOIUrl":"10.1016/j.redox.2025.103856","url":null,"abstract":"<div><div>Oxidatively damaged DNA caused by reactive oxygen species (ROS) in the fetal brain contributes to neurodevelopmental disorders (NDDs), but the mechanism is unclear. We investigated the impact of this DNA damage on the developing fetal brain using a DNA repair-deficient oxoguanine glycosylase 1 (<em>Ogg1</em>) knockout (KO) mouse model, exposed during pregnancy to physiological (saline)- and ethanol (EtOH)-enhanced ROS levels. Oxidatively damaged DNA in saline-exposed <em>Ogg1</em> KO vs. wild-type (WT) fetal brains was increased, and further enhanced by EtOH exposure. These OGG1-and EtOH-dependent patterns of DNA damage were reflected in: (a) increased gene dysregulation in saline-exposed KO brains, and greatly exacerbated by EtOH, notably in the long-term synaptic potentiation pathway, crucial for learning and memory; (b) impaired mitochondrial metabolism in cultured primary <em>Ogg1</em> KO neurons; and, (c) sex-dependent learning and memory disorders. These results suggest oxidatively damaged DNA in DNA repair-deficient fetal brains contributes to NDDs by altering gene expression and mitochondrial metabolism.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103856"},"PeriodicalIF":11.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}