Redox Biology最新文献

{"title":"Non-canonical activation of VEGFA through TIMM44-dependent mitochondrial remodelling.","authors":"Tanvi Chaudhary, Sharath Mohan Bhat, Priyadarshika Pradhan, Manjunath B Joshi, Devanjan Sinha","doi":"10.1016/j.redox.2026.104381","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104381","url":null,"abstract":"<p><p>Coordination of mitochondrial functional states with nuclear transcriptional programs remain critical for cellular adaptation. Here, we identify mitochondrial protein import capacity as a regulator of redox-dependent signalling in tumour cells. We show that the mitochondrial import motor component TIMM44, which is upregulated in angiogenesis-driven tumours, drives respiratory remodelling without increasing mitochondrial abundance. This mitochondrial reprogramming establishes a redox-competent state that activates ASK1-p38MAPK, resulting in SP1-dependent upregulation of VEGFA independently of HIF stabilization. Importantly, induction of mitochondrial biogenesis via PGC-1α fails to recapitulate this response despite increased active mitochondrial content, demonstrating that abundance of active mitochondria or generic metabolic activation is insufficient to drive this HIF-independent transcription. Collectively, our findings identify mitochondrial protein import process as an active signalling regulator rather than a passive housekeeping role, which links mitochondrial proteostasis to redox-sensitive kinase activation and transcriptional control. This work highlights a non-canonical mitochondrial signalling mechanism through which cells couple organelle remodelling to gene expression programs.</p>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"97 ","pages":"104381"},"PeriodicalIF":16.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892384","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":"Monodehydroascorbate reductases in plants: integrating ascorbate recycling, redox signaling, and stress adaptation","authors":"Yuxin Xiao, Jiatong Zhou, Shengchun Li","doi":"10.1016/j.redox.2026.104382","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104382","url":null,"abstract":"Reactive oxygen species (ROS) are central regulators of plant growth, development, and environmental adaptation, with hydrogen peroxide (H<ce:inf loc=\"post\">2</ce:inf>O<ce:inf loc=\"post\">2</ce:inf>) acting as a key signaling molecule. The ascorbate-glutathione cycle is the major antioxidant pathway that maintains H<ce:inf loc=\"post\">2</ce:inf>O<ce:inf loc=\"post\">2</ce:inf> homeostasis, and monodehydroascorbate reductase (MDHAR) plays a critical role by regenerating reduced ascorbate (ASC) from monodehydroascorbate (MDHA). Although traditionally viewed as an ASC-recycling enzyme, increasing evidence indicates that MDHAR has broader functions in redox regulation. Recent studies have revealed that MDHAR contributes to stress responses, developmental regulation, and ROS signaling through mechanisms that cannot be fully explained by ASC recycling alone. In this review, we summarize recent advances in the structural characteristics, regulation, subcellular specialization, and evolution of plant MDHARs. We also discuss emerging non-canonical functions of MDHAR, alternative pathways for MDHA reduction, and the mechanistic basis for the contrasting effects of MDHAR manipulation on ASC accumulation. Finally, we propose that MDHAR functions as an integrative hub linking ascorbate metabolism with cellular redox networks and highlight key challenges and future opportunities for exploiting MDHAR to improve crop stress tolerance, productivity, and nutritional quality.","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"13 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148884855","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":"A novel Keap1-Nrf2 inhibitor 6K delays the progression of AKI-to-CKD by mitigating maladaptive repair","authors":"Yiming Wang, Yi Sun, Ting Zhou, Cai Gao, Jihan Liu, Zhicong Chen, PanShuang Qiao, Guangying Shao, Min Li, Baoxue Yang, Chunlin Zhuang, Hong Zhou","doi":"10.1016/j.redox.2026.104374","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104374","url":null,"abstract":"Severe or recurrent acute kidney injury (AKI) is a critical risk factor for chronic kidney disease (CKD) progression, characterized by irreversible fibrosis and limited therapeutic options. Maladaptive repair in proximal tubular epithelial cells (PTECs) during AKI-to-CKD progression is crucial, with the oxidative stress (OS)-ferroptosis axis emerging as a potential therapeutic target. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of redox balance and ferroptosis, is essential for cellular homeostasis, but its role in PTECs maladaptive repair is unclear. In this study, we employed Nrf2 knockout (KO) mice to establish an AKI-to-CKD model through bilateral ischemia-reperfusion injury (bIRI). Nrf2 deficiency significantly exacerbated renal fibrosis, OS markers (H<ce:inf loc=\"post\">2</ce:inf>O<ce:inf loc=\"post\">2</ce:inf>, NOX4, 8-OHdG), and ferroptosis indicators (4-HNE, MDA, ACSL4), while concurrently suppressing antioxidant enzyme activity (SOD, GPx) and the expression of maladaptive repair-related genes (<ce:italic>Vcam1</ce:italic>, <ce:italic>Irf8</ce:italic>, etc.). Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were significantly elevated in KO mice. We found increased oxidative and inflammatory markers in CKD patients' serum and urine, highlighting the role of OS in disease progression. Treatment with 6K, a Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) inhibitor, markedly improved renal function, suppressed OS and ferroptosis, and upregulated adaptive repair-related genes and downregulated maladaptive repair-related genes in bIRI mice. Compound 6K exhibited a kidney-targeted distribution profile, with an area under the concentration-time curve (AUC) kidney/AUC blood ratio of 1.01, suggesting its potential for targeted treatment of kidney diseases. In human kidney-2 (HK-2) cells, 6K activated the Nrf2-GPX4 axis, thereby alleviated RSL3-induced suppression of GPX4 expression, reduced reactive oxygen species (ROS) accumulation and lipid peroxidation, and mitigated ferroptosis. Furre, 6K treatment significantly delayed fibrosis progression in bIRI and unilateral ureteral obstruction (UUO) models. In summary, our findings demonstrate that Nrf2 deficiency exacerbates AKI-CKD progression through redox imbalance and ferroptosis-mediated maladaptive repair. Targeting Keap1-Nrf2 with 6K protects against renal injury and fibrosis, highlighting its therapeutic potential for kidney diseases.","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"18 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148884856","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":"Targeting 3-mercaptopyruvate sulfurtransferase selectively eliminates colorectal cancer stem cells.","authors":"Kelly Ascenção, Olivia Oravecz, Csaba Szabo","doi":"10.1016/j.redox.2026.104376","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104376","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) contribute to therapeutic resistance, metastatic progression, and tumor recurrence, yet the metabolic pathways that sustain their survival remain incompletely understood. Here, we identify 3-mercaptopyruvate sulfurtransferase (3-MST), a hydrogen sulfide-producing enzyme encoded by MPST, as a metabolic dependency of colorectal CSCs. 3-MST expression was increased in human colorectal tumors and cancer cell lines and strongly correlated with proliferative capacity. HCT116-derived CSCs exhibited elevated 3-MST expression, increased hydrogen sulfide and reactive sulfur species production, altered membrane rigidity, and a metabolically restrained phenotype characterized by low basal oxidative phosphorylation and glycolysis. Genetic depletion of 3-MST preferentially impaired CSC proliferation, spheroid formation, stem-like properties, and migration, with less pronounced effects in differentiated parental cells. Pharmacological inhibition of 3-MST reproduced these effects across CSCs derived from several colorectal cancer cell lines and induced near-complete suppression of mitochondrial respiration and glycolytic activity. 3-MST inhibition also increased membrane fluidity, promoted cell death, and reduced CSC-derived tumor growth in mice. Integrated transcriptomic, proteomic, metabolomic, and lipidomic analyses demonstrated coordinated disruption of mitochondrial carbon metabolism, respiratory-chain maintenance, lipid desaturation, and membrane phospholipid homeostasis. These changes were accompanied by accumulation of free fatty acids and diacylglycerols and activation of antioxidants, integrated stress-response, endoplasmic-reticulum-stress, apoptotic, and p53-associated pathways. Ferroptosis-related molecular signatures were also enriched. These findings identify 3-MST as a critical regulator of colorectal CSC bioenergetics and membrane homeostasis and reveal a therapeutically exploitable metabolic vulnerability in treatment-resistant colorectal cancer.</p>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"97 ","pages":"104376"},"PeriodicalIF":16.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897752","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":"Hepatic methanethiol oxidase (MTO) activity of mice requires adequate dietary supply of copper","authors":"Niklas Krafczyk,Kristina Lossow,Lara Biegel,Nora Meinhardt,Maria Schwarz,Hans Zischka,Holger Steinbrenner,Anna Patricia Kipp,Lars-Oliver Klotz","doi":"10.1016/j.redox.2026.104384","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104384","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"369 1","pages":"104384"},"PeriodicalIF":11.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893690","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":"Inter-domain distance analysis reveals conformational changes in the Keap1-Nrf2 stress sensor system","authors":"Ritsumi Saito, Takeshi Kawabata, Seisuke Yamashita, Keisuke Oki, Takashi Fujii, Hiroki Kawauchi, Yoshiaki Doi, Machiko Irie, Takuya Torizawa, Kengo Kinoshita, Masayuki Yamamoto, Seizo Koshiba","doi":"10.1016/j.redox.2026.104379","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104379","url":null,"abstract":"The Keap1-Nrf2 system plays a central role in cellular defense against oxidative stress. Structural information on full-length Keap1 is essential for understanding the molecular basis of this regulation. However, its overall architecture has remained elusive due to pronounced conformational flexibility. In this study, we performed single-particle cryo-electron microscopy (cryo-EM) analysis of full-length Keap1 and found multiple particle conformations accompanied by severe preferred orientation in vitrified ice. To address these problems, we developed an analytical system that focuses on measuring the inter-domain distance between the two DC domains of the Keap1 homodimer. Using this approach, we identified the change of inter-domain distance distributions of Keap1 induced by Nrf2 binding or its inhibition, suggesting that these conformational changes are associated with Nrf2 regulation. Furthermore, through integration of this system with Keap1 deletion mutants, three flexible regions within Keap1 are found to contribute substantially to the conformational flexibility of the Keap1 homodimer. Together, these findings provide structural insights into the dynamic changes of the Keap1-Nrf2 system that would contribute to the development of Keap1-targeted therapeutics.","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"70 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148884858","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":"A ROS-Responsive Platelet Extracellular Vesicle Biomimetic Nanosystem Regulates CD36/Fyn-CXCL-NETosis Pathway-Mediated Immune-Inflammatory Amplification in the Treatment of Transfusion-Related Acute Lung Injury","authors":"Jiani Gao,Ke Zhou,Yijiu Ren,Fengjing Yang,Minjue Shan,Yubing Fang,Changbo Sun,Weili Han,Chang Chen,Xuefei Hu","doi":"10.1016/j.redox.2026.104375","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104375","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"24 1","pages":"104375"},"PeriodicalIF":11.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893691","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":"NRF2 activation is required for chemotherapy resistance acquisition in medulloblastoma via metabolic and redox adaptation","authors":"Lorenzo Manfreda,Fatlum Rruga,Arianna Zanolli,Bryan Marzullo,Lisa Vettore,Martina Mozzo,Martina Canton,Chiara Marchioro,Elena Rampazzo,Elena Mariotto,Serena Filiberti,Marta Turati,Roberto Ronca,Daniel A. Tennant,Luca Persano,Giampietro Viola,Roberta Bortolozzi","doi":"10.1016/j.redox.2026.104380","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104380","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"28 1","pages":"104380"},"PeriodicalIF":11.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893692","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":"Corrigendum to \"Degenerate cysteine patterns mediate two redox sensing mechanisms in the papillomavirus E7 oncoprotein\" [Redox Biol. 11 (2017) 38-50].","authors":"Gabriela Camporeale, Juan R Lorenzo, Maria G Thomas, Edgardo Salvatierra, Silvia S Borkosky, Marikena G Risso, Ignacio E Sánchez, Gonzalo de Prat Gay, Leonardo G Alonso","doi":"10.1016/j.redox.2026.104367","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104367","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":" ","pages":"104367"},"PeriodicalIF":16.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874858","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":"Corrigendum to \"Regulation of PD-L1 expression in K-ras-driven cancers through ROS-mediated FGFR1 signaling\" [Redox Biol. 38, (2021), 101780].","authors":"Christophe Glorieux, Xiaojun Xia, Yong-Qiao He, Yumin Hu, Kelly Cremer, Annie Robert, Junchen Liu, Fen Wang, Jianhua Ling, Paul J Chiao, Peng Huang","doi":"10.1016/j.redox.2026.104371","DOIUrl":"https://doi.org/10.1016/j.redox.2026.104371","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":" ","pages":"104371"},"PeriodicalIF":16.2,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851033","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}