Redox Biology最新文献

{"title":"Phytochemical nanozymes reprogram redox for balanced antimicrobial and regenerative therapy in acute and chronic diabetic wounds","authors":"Yipeng Pang ,&nbsp;Fructueux Modeste Amona ,&nbsp;Xiaohan Chen ,&nbsp;Yuxin You ,&nbsp;Ziqi Sha ,&nbsp;Zilu Liu ,&nbsp;Jiamin Li ,&nbsp;Yi Liu ,&nbsp;Xingtang Fang ,&nbsp;Xi Chen","doi":"10.1016/j.redox.2025.103718","DOIUrl":"10.1016/j.redox.2025.103718","url":null,"abstract":"<div><div>Chronic diabetic wounds are characterized by persistent oxidative stress and microbial infections, leading to delayed healing and tissue repair. While elevated reactive oxygen species (ROS) levels can provide bactericidal effects, uncontrolled oxidative stress simultaneously impairs tissue regeneration. Thus, precise redox modulation that balances antimicrobial efficacy with tissue regeneration is critical for effective wound therapy. Herein, we developed a phytochemical nanozymes system by integrating ferulic acid (FA) with cerium oxide nanoparticles (CeO₂), enabling precise redox modulation to balance antimicrobial efficacy with tissue regeneration. Structural analysis confirmed the uniform dispersion and pH-responsive release of FA and Ce ions, facilitating targeted redox modulation. The FA-CeO₂ nanozymes exhibited potent antioxidant activity through Ce³⁺/Ce⁴⁺ cycling and FA-mediated radical scavenging, effectively mitigating oxidative stress while promoting bacterial clearance against <em>S. aureus</em> and <em>E. coli</em>. Furthermore, FA-CeO₂ significantly enhanced Nrf2/HO-1 pathway activation, leading to upregulated VEGF/CD31 expression, accelerated cell proliferation, and enhanced collagen deposition <em>in vitro</em>. <em>In vivo</em>, FA-CeO₂ facilitated wound closure, reduced bacterial burden, and improved tissue regeneration in acute and diabetic wound models, with minimal cytotoxicity and excellent biocompatibility. These findings highlight the critical role of precise redox modulation in balancing antibacterial and regenerative therapy, positioning phytochemical nanozymes as a dual-modality platform for effective wound therapy and advancing nanomedicine strategies targeting oxidative stress and tissue repair.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103718"},"PeriodicalIF":10.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271779","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":"Long-term senolytic therapy with Dasatinib and Quercetin alleviates lipofuscin-dependent retinal degeneration in mice","authors":"Bo Yang ,&nbsp;Kunhuan Yang ,&nbsp;Ruitong Xi ,&nbsp;Shiying Li ,&nbsp;Jingmeng Chen ,&nbsp;Yalin Wu","doi":"10.1016/j.redox.2025.103716","DOIUrl":"10.1016/j.redox.2025.103716","url":null,"abstract":"<div><div>Dry age-related macular degeneration (AMD) is one of the common blinding eye diseases, with pathological hallmarks of lipofuscin accumulation, neuroretina atrophy and retinal pigment epithelium (RPE) degeneration. Currently, there are no effective interventions for dry AMD. Although there is already evidence suggesting a link between cellular senescence and age-related diseases, it is still unclear whether long-term senolytic therapy with Dasatinib and Quercetin (D + Q) can slow the progression of dry AMD and ultimately prevent retinal structural damage and function loss. Mice lacking the <em>Abca4</em> and <em>Rdh8</em> genes (<em>Abca4</em>^{<em>−/−</em>}<em>Rdh8</em>^{<em>−/−</em>} mice) are a preclinical model of dry AMD. In this study, we performed a 4-month senolytic therapy with D + Q on 4-month-old <em>Abca4</em>^{<em>−/−</em>}<em>Rdh8</em>^{<em>−/−</em>} mice. <em>Abca4</em>^{<em>−/−</em>}<em>Rdh8</em>^{<em>−/−</em>} mice at the age of 8 months showed obvious retinal degeneration, along with RPE senescence, lysosomal alkalinization, lipofuscin accumulation and oxidative stress. Importantly, the long-term D + Q regimen significantly alleviated the degeneration of retinal structures and function in 8-month-old <em>Abca4</em>^{<em>−/−</em>}<em>Rdh8</em>^{<em>−/−</em>} mice, and it effectively repressed cellular senescence, lysosomal alkalinization, lipofuscin accumulation and oxidative stress in the RPE. This study is the first to demonstrate the effect of long-term intervention with senolytics D + Q on dry AMD. Overall, these findings highlight the potential of long-term senolytic treatment as an intervention for dry AMD.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103716"},"PeriodicalIF":10.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239636","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":"Sex-specific metabolic responses to high-fat diet in mice with NOX4 deficiency","authors":"Jacob M. Bond ,&nbsp;Martina Dzubanova ,&nbsp;Adele K. Addington ,&nbsp;Charles P. Najt ,&nbsp;Elizabeth R. Gilbert ,&nbsp;Michaela Tencerova ,&nbsp;Siobhan M. Craige","doi":"10.1016/j.redox.2025.103698","DOIUrl":"10.1016/j.redox.2025.103698","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) are critical mediators of cellular signaling that regulate metabolic homeostasis, including lipid uptake, synthesis, and storage. NADPH oxidase 4 (NOX4), a significant enzymatic source of ROS, has been identified as a redox-sensitive regulator of glucose and lipid metabolism. However, its contribution to sex-specific metabolic regulation remains poorly defined. This study compared how NOX4 knock-out (NOX4 KO) shifted systemic and tissue-specific metabolic phenotypes between male and female mice fed with a high-fat diet (HFD) for 20-weeks. We observed that male NOX4 mice on HFD exhibited reduced adiposity, diminished liver lipid accumulation, and improved glucose and insulin tolerance compared to male WT mice on HFD. In contrast, female NOX4 KO mice developed increased adiposity and lipid accumulation in peripheral adipose depots, accompanied by impaired glucose tolerance. Gene expression profiling in skeletal muscle and liver revealed distinct, sex-specific patterns of changes in genes related to lipid uptake, synthesis, and storage, possibly implicating differential activation of PPAR signaling pathways supportive of <em>in vivo</em> data. These findings identify NOX4 as a central regulator of sexually dimorphic lipid metabolism, acting through redox-sensitive transcriptional networks to shape divergent metabolic responses to HFD.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103698"},"PeriodicalIF":10.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279210","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":"Retraction notice to “Curcumin blunts epithelial-mesenchymal transition of hepatocytes to alleviate hepatic fibrosis through regulating oxidative stress and autophagy” [Redox Biology 36 (2020) 101600]","authors":"Desong Kong ,&nbsp;Zili Zhang ,&nbsp;Liping Chen ,&nbsp;Weifang Huang ,&nbsp;Feng Zhang ,&nbsp;Ling Wang ,&nbsp;Yu Wang ,&nbsp;Peng Cao ,&nbsp;Shizhong Zheng","doi":"10.1016/j.redox.2025.103690","DOIUrl":"10.1016/j.redox.2025.103690","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"84 ","pages":"Article 103690"},"PeriodicalIF":10.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226430","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":"Nitric Oxide restricts iron availability and induces quorum sensing in Streptococcus pyogenes","authors":"Ian E. McIntire ,&nbsp;Venkatesan Kathiresan ,&nbsp;Brian Hoffman ,&nbsp;Jennifer Chang ,&nbsp;Michael J. Federle ,&nbsp;Douglas D. Thomas","doi":"10.1016/j.redox.2025.103699","DOIUrl":"10.1016/j.redox.2025.103699","url":null,"abstract":"<div><div>Nitric oxide (NO) is a free radical signaling molecule with multiple biological functions. As part of the innate immune system, NO has antimicrobial properties playing an important role in host defense. Mechanisms of NO cytotoxicity result from its ability to bind metals and inhibit enzyme function or by increasing nitrosative and oxidative stress within cells. One of the primary biological targets of NO is the chelatable iron pool (CIP) which is quantitatively converted to dinitrosyliron complexes (DNIC) when it reacts with NO. Despite the numerous purported mechanisms attributed to NO's bactericidal properties, DNIC formation and its ability to restrict iron bioavailability from pathogenic bacteria has not been directly tested. <em>Streptococcus pyogenes</em> is a human pathogen that causes a range of diseases spanning from pharyngitis and impetigo to soft tissue necrosis and toxic shock. <em>S. pyogenes</em> employs the Rgg2/Rgg3 quorum sensing (QS) system to regulate aspects of its virulence potential, including biofilm formation, lysozyme resistance, and modulation of host innate immune response. Previous studies found that iron and manganese restriction induced Rgg2/Rgg3 QS, leading us to test whether NO-dependent iron restriction mediated by DNIC formation was sufficient to induce QS and related iron-starvation phenotypes. Here, we demonstrate that DNIC are formed in <em>S. pyogenes</em> exposed to physiologically relevant NO concentrations. The DNIC are formed from the CIP, and formation led to a significant reduction in the CIP, which correlated to a concomitant activation of QS and iron-regulated gene expression. These studies are the first to demonstrate that restriction of iron bioavailability mediated by DNIC formation is a functional mechanism by which NO can regulate QS, gene expression, and cell growth in bacteria.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103699"},"PeriodicalIF":10.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237365","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":"Radiation-induced upregulation of itaconate in macrophages promotes the radioresistance of non-small cell lung cancer by stabilizing NRF2 protein and suppressing immune response","authors":"Mengjie Che ,&nbsp;Wenwen Wei ,&nbsp;Xiao Yang ,&nbsp;Jinzi Liang ,&nbsp;Yan Li ,&nbsp;Ying Ye ,&nbsp;Yajie Sun ,&nbsp;Yan Hu ,&nbsp;Zhanjie Zhang ,&nbsp;You Qin ,&nbsp;Jing Huang ,&nbsp;Bian Wu ,&nbsp;Haibo Zhang ,&nbsp;Kunyu Yang ,&nbsp;Chao Wan ,&nbsp;Lu Wen","doi":"10.1016/j.redox.2025.103711","DOIUrl":"10.1016/j.redox.2025.103711","url":null,"abstract":"<div><div>Radioresistance is one of the important reasons for local recurrence and distant metastasis in non-small cell lung cancer (NSCLC). Itaconate primarily functions as an anti-inflammatory metabolite in macrophages, however, its role in radiotherapy remains to be explored. In this study, we demonstrated that radiation significantly increases itaconate in the tumor microenvironment (TME), which is produced by macrophages. Mechanistically, the NF-κB signaling pathway is rapidly activated in macrophages, which enhances the binding of P65 to the <em>Acod1</em> promoter region, leading to significantly increased secretion of itaconate. Excessive itaconate alleviates oxidative stress of NSCLC cell lines by stabilizing NRF2 protein. Notably, specifically knocking out <em>Acod1</em> on myeloid cells enhances the activation of the tumor immune microenvironment in response to radiotherapy, particularly increasing the infiltration and activation of CD8⁺ T cells. Therefore, we propose that targeting Acod1 could be an effective strategy to improve radiosensitivity in NSCLC.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103711"},"PeriodicalIF":10.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231187","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":"PATJ regulates cell stress responses and vascular remodeling post-stroke","authors":"Mengqi Zhang ,&nbsp;Wei I. Jiang ,&nbsp;Kajsa Arkelius ,&nbsp;Raymond A. Swanson ,&nbsp;Dengke K. Ma ,&nbsp;Neel S. Singhal","doi":"10.1016/j.redox.2025.103709","DOIUrl":"10.1016/j.redox.2025.103709","url":null,"abstract":"<div><div>PALS1-associated tight junction (PATJ) protein is linked to metabolic disease and stroke in human genetic studies. Despite the recognized role of PATJ in cell polarization, its specific functions in metabolic disease and ischemic stroke recovery remain largely unexplored. We explored the functions of PATJ in an <em>in vitro</em> model and in vivo in <em>C. elegans</em> and mice. Using a mouse model of stroke, we found post-ischemic stroke duration-dependent increase of PATJ abundance in endothelial cells. PATJ knock-out (KO) HEK293 cells generated by CRISPR-Cas9 suggest roles for PATJ in cell proliferation, migration, mitochondrial stress response, and interactions with the Yes-associated protein (YAP)-1 signaling pathway. Notably, <em>PATJ</em> deletion altered YAP1 nuclear translocation. <em>PATJ</em> KO cells demonstrated transcriptional reprogramming based on RNA sequencing analysis, and identified dysregulation in genes central to vascular development, stress response, and metabolism, including <em>RUNX1</em>, <em>HEY1</em>, <em>NUPR1</em>, and <em>HK2</em>. Furthermore, we found that <em>mpz-1</em>, the homolog of PATJ, was significantly upregulated under hypoxic conditions in <em>C. elegans</em>. Knockdown of <em>mpz-1</em> resulted in abnormal neuronal morphology and increased mortality, both of which were exacerbated by hypoxia exposure, indicating a critical protective role of PATJ/MPZ-1 in maintaining neuronal integrity and survival, particularly during oxygen deprivation stress relevant to ischemic stroke. These insights offer a new understanding of PATJ's regulatory functions within cellular and vascular physiology and help lay the groundwork for therapeutic strategies targeting PATJ-mediated pathways for stroke rehabilitation and neurovascular repair.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103709"},"PeriodicalIF":10.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212329","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":"Silicon-enriched meat consumption mitigates brain cortex damage associated with diabetic dyslipidemia in a late-stage type 2 diabetes mellitus rat model","authors":"Rocío Redondo-Castillejo ,&nbsp;Luis Apaza Ticona ,&nbsp;Adrián Macho-González ,&nbsp;Aránzazu Bocanegra ,&nbsp;Alba Garcimartín ,&nbsp;Marina Hernández-Martín ,&nbsp;Anastasia Parfenova ,&nbsp;Sara Bastida ,&nbsp;Luis García-García ,&nbsp;M. Elvira López-Oliva ,&nbsp;Francisco J. Sánchez-Muniz ,&nbsp;Juana Benedí","doi":"10.1016/j.redox.2025.103697","DOIUrl":"10.1016/j.redox.2025.103697","url":null,"abstract":"<div><div>Neuroprotective properties of silicon have been reported, particularly in mitigating dementia and Alzheimer's disease due to its ability to reduce aluminum bioavailability. However, its potential as a nutritional adjuvant in reducing brain damage associated with hypercholesterolemia and central insulin resistance (IR) in late-stage type 2 diabetes mellitus (T2DM) remains unexplored. This study aimed to evaluate the effects of silicon-enriched meat (Si-RM) on the brain cortex of T2DM rats. Rat models of early-stage-T2DM (ED) (n = 8) and late-stage-T2DM (LD) (n = 16) were induced by high-saturated fat diet and high-saturated fat high-cholesterol diet plus streptozotocin/nicotinamide injection, respectively. A control meat (C-RM) was included in the diet of both ED and LD groups. Finally, after confirming hyperglycemia in LD rats, the C-RM was replaced by Si-RM in half of the animals for the last five weeks of the study, obtaining the LD-Si group (n = 8), while the other half continued eating C-RM. In LD rats pathological outcomes included: harmful oxysterol profile, decreased antioxidant defenses, neuroinflammation, brain IR, augmented glucose uptake and impaired cholinergic transmission. Si-RM consumption ameliorates these key outcomes by reducing brain levels of pro-oxidant oxysterols (25-OHC and 27-OHC) to levels of ED rats. Antioxidant defenses, including SOD and arylesterase activity, were enhanced, and inflammatory markers, such as GFAP, IL6, and TNFα, were reduced compared to LD and ED counterparts. Notably, silicon restored brain insulin signaling, normalized glucose uptake via GLUT3, and shifted to an acetylcholine-preserving profile, significantly mitigating neurodegenerative risks. This study demonstrates for the first time that silicon, provided as a functional dietary ingredient of meat-products, exhibited a capacity to partially counteract brain cortex metabolic damage caused by T2DM.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103697"},"PeriodicalIF":10.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231325","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":"Hsp90 C-terminal domain inhibition enhances ferroptosis by disrupting GPX4-VDAC1 interaction to increase HMOX1 release from oligomerized VDAC1 channels","authors":"Jieyou Li ,&nbsp;Guibing Wu ,&nbsp;Hairou Su ,&nbsp;Manfeng Liang ,&nbsp;Shengpei Cen ,&nbsp;Yandan Liao ,&nbsp;Xiangjun Zhou ,&nbsp;Guantai Xie ,&nbsp;Zihao Deng ,&nbsp;Wenchong Tan ,&nbsp;Yan Li ,&nbsp;Wang Xiao ,&nbsp;Lixia Liu ,&nbsp;Jinxin Zhang ,&nbsp;Zhenming Zheng ,&nbsp;Yaotang Deng ,&nbsp;Yaling Huang ,&nbsp;Xiongjie Shi ,&nbsp;Yilin Liu ,&nbsp;Guowei Zhang ,&nbsp;Xuemei Chen","doi":"10.1016/j.redox.2025.103672","DOIUrl":"10.1016/j.redox.2025.103672","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide. Given the critical role of liver in iron storage and metabolism, ferroptosis, characterized by iron-dependent lipid peroxidation and oxidative damage, has become a potential therapy for HCC. Recent research indicated that Voltage-dependent anion-selective channel protein 1 (VDAC1), a key gatekeeper on the outer mitochondrial membrane (OMM), promotes ferroptosis in its oligomeric form. While oxidative stress is known to promote VDAC1 oligomerization, the relationship between oxidative modifications such as carbonylation and VDAC1 oligomerization remains poorly understood. Additionally, it is uncertain whether oligomerized VDAC1 channels facilitate the release of ferroptosis-related molecules. Our research discovered that the inhibition of the C-terminal domain of Heat shock protein 90 (Hsp90) reduced the protein level of Glutathione peroxidase 4 (GPX4) and decreased the interaction between GPX4 and VDAC1, consequently activating the carbonylation and oligomerization of VDAC1 through VDAC1-K274 site in a redox-dependent manner. The VDAC1 oligomerization promotes the release of Heme oxygenase-1 (HMOX1) from mitochondria into the cytoplasm, leading to iron overload and ultimately promoting ferroptosis. Thus, VDAC1 oligomerization is a critical factor in the pathway linking mitochondrial dysfunction to ferroptosis, highlighting the potential therapeutic interventions for HCC associated with iron dysregulation.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"85 ","pages":"Article 103672"},"PeriodicalIF":10.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204776","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":"Crosstalk of autophagy and ferroptosis in cardiovascular diseases: from pathophysiology to novel therapy","authors":"Changhao Hu ,&nbsp;Siying Gao ,&nbsp;Xinyi Li ,&nbsp;Kaiqing Yang ,&nbsp;Ye Cheng,&nbsp;Wei Guo,&nbsp;Huijun Wu,&nbsp;Xueqin Cheng,&nbsp;Weiwen Zhao,&nbsp;Yuxuan Kong,&nbsp;Haoyuan Hu,&nbsp;Songyun Wang","doi":"10.1016/j.redox.2025.103705","DOIUrl":"10.1016/j.redox.2025.103705","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs) are characterized by high morbidity and mortality rates, imposing substantial epidemiological and economic burdens worldwide. Among the multifaceted mechanisms implicated in CVDs, autophagy and ferroptosis, two intimately linked cellular processes, emerge as pivotal pathophysiological contributors. Autophagy, as an evolutionary conserved process that mediates the degradation and recycling of intracellular components, including proteins and organelles, exerts critical regulatory effects on iron metabolism and lipid homeostasis through various specialized forms, including ferritinophagy and lipophagy. Conversely, ferroptosis, an iron dependent form of cell death, involves oxidative stress and the accumulation of lipid peroxides, often triggered by iron overload and the dysfunction of glutathione peroxidase 4 (GPX4). The intricate crosstalk between these two processes, particularly ferritinophagy-mediated iron regulation influencing ferroptosis, plays a crucial role in diverse CVDs contexts. Key regulatory molecules, such as Beclin-1 and nuclear factor E2-related factor 2 (Nrf2), function as central hubs, orchestrating the intricate interplay between autophagy and ferroptosis. Through a comprehensive examination of these mechanisms across various CVDs pathologies, we summarize the latest findings and outline potential therapeutic strategies targeting the crosstalk between autophagy and ferroptosis. As the inaugural review focusing on autophagy-ferroptosis interactions in CVDs, this work significantly enriches our understanding of the pathophysiology of CVDs and identifies novel therapeutic targets with potential for precision medicine interventions in managing CVDs.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"84 ","pages":"Article 103705"},"PeriodicalIF":10.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185308","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}