Redox Biology最新文献

{"title":"Effect of alternative oxidase (AOX) expression on mouse cerebral mitochondria bioenergetics","authors":"Belem Yoval-Sánchez ,&nbsp;Ivan Guerrero ,&nbsp;Fariha Ansari ,&nbsp;Zoya Niatsetskaya ,&nbsp;Max Siragusa ,&nbsp;Jordi Magrane ,&nbsp;Vadim Ten ,&nbsp;Csaba Konrad ,&nbsp;Marten Szibor ,&nbsp;Alexander Galkin","doi":"10.1016/j.redox.2024.103378","DOIUrl":"10.1016/j.redox.2024.103378","url":null,"abstract":"<div><div>Alternative oxidase (AOX) is an enzyme that transfers electrons from reduced quinone directly to oxygen without proton translocation. When AOX from <em>Ciona intestinalis</em> is xenotopically expressed in mice, it can substitute the combined electron-transferring activity of mitochondrial complexes III/IV. Here, we used brain mitochondria from AOX-expressing mice with such a chimeric respiratory chain to study respiratory control bioenergetic mechanisms.</div><div>AOX expression did not compromise the function of the mammalian respiratory chain at physiological conditions, however the complex IV inhibitor cyanide only partially blocked respiration by AOX-containing mitochondria. The relative fraction of cyanide-insensitive respiration increased at lower temperatures, indicative of a temperature-controlled attenuation of mammalian respiratory enzyme activity.</div><div>As AOX does not translocate protons, the mitochondrial transmembrane potential in AOX-containing mitochondria was more sensitive to cyanide during succinate oxidation than during malate/pyruvate-supported respiration. High concentrations of cyanide fully collapsed membrane potential during oxidation of either succinate or glycerol 3-phosphate, but not during malate/pyruvate-supported respiration. This confirms AOX's electroneutral redox activity and indicates differences in the proton-translocating capacity of dehydrogenases upstream of the ubiquinone pool. Our respiration data refutes previous proposals for quinone partitioning within the supercomplexes of the respiratory chain, instead supporting the concept of a single homogeneous, freely diffusing quinone pool.</div><div>Respiration with either succinate or glycerol 3-phosphate promotes reverse electron transfer (RET) towards complex I. AOX expression significantly decreased RET-induced ROS generation, with the effect more pronounced at low temperatures. Inhibitor-sensitivity analysis showed that the AOX-induced decrease in H₂O₂ release is due to the lower contribution of complex I to net ROS production during RET.</div><div>Overall, our findings provide new insights into the role of temperature as a mechanism to control respiration and highlight the utility of AOX as a genetic tool to characterize both the distinct pathways of oxygen reduction and the role of redox control in RET.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103378"},"PeriodicalIF":10.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury","authors":"Xue-Xue Zhu ,&nbsp;Xiao Fu ,&nbsp;Xin-Yu Meng ,&nbsp;Jia-Bao Su ,&nbsp;Guan-Li Zheng ,&nbsp;An-Jing Xu ,&nbsp;Guo Chen ,&nbsp;Yuan Zhang ,&nbsp;Yao Liu ,&nbsp;Xiao-Hui Hou ,&nbsp;Hong-Bo Qiu ,&nbsp;Qing-Yi Sun ,&nbsp;Jin-Yi Hu ,&nbsp;Zhuo-Lin Lv ,&nbsp;Yao Wang ,&nbsp;Hai-Bin Jiang ,&nbsp;Neng Bao ,&nbsp;Zhi-Jun Han ,&nbsp;Qing-Bo Lu ,&nbsp;Hai-Jian Sun","doi":"10.1016/j.redox.2024.103373","DOIUrl":"10.1016/j.redox.2024.103373","url":null,"abstract":"<div><div>The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal <em>Parabacteroides goldsteinii</em> (<em>P. goldsteinii</em>) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of <em>P. goldsteinii</em> and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of <em>P. goldsteinii</em>. Our results shed light on the role of intestinal microbiota <em>P. goldsteinii</em> and serum metabolites dodecafluorpentan in CR benefits to AKI.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103373"},"PeriodicalIF":10.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial CR3 promotes neuron ferroptosis via NOX2-mediated iron deposition in rotenone-induced experimental models of Parkinson's disease","authors":"Qinghui Wang ,&nbsp;Jianing Liu ,&nbsp;Yu Zhang ,&nbsp;Zhen Li ,&nbsp;Zirui Zhao ,&nbsp;Wanwei Jiang ,&nbsp;Jie Zhao ,&nbsp;Liyan Hou ,&nbsp;Qingshan Wang","doi":"10.1016/j.redox.2024.103369","DOIUrl":"10.1016/j.redox.2024.103369","url":null,"abstract":"<div><div>The activation of complement receptor 3 (CR3) in microglia contributes to neurodegeneration in neurological disorders, including Parkinson's disease (PD). However, it remains unclear for mechanistic knowledge on how CR3 mediates neuronal damage. In this study, the expression of CR3 and its ligands iC3b and ICAM-1 was found to be up-regulated in the midbrain of rotenone PD mice, which was associated with elevation of iron content and disruption of balance of iron metabolism proteins. Interestingly, genetic deletion of CR3 blunted iron accumulation and recovered the expression of iron metabolism markers in response to rotenone. Furthermore, reduced lipid peroxidation, ferroptosis of dopaminergic neurons and neuroinflammation were detected in rotenone-lesioned CR3^−/− mice compared with WT mice. The regulatory effect of CR3 on ferroptotic death of dopaminergic neurons was also mirrored <em>in vitro</em>. Mechanistic study revealed that iron accumulation in neuron but not the physiological contact between microglia and neurons was essential for microglial CR3-regulated neuronal ferroptosis. In a cell-culture system, microglial CR3 silence significantly dampened iron deposition in neuron in response to rotenone, which was accompanied by mitigated lipid peroxidation and neurodegeneration. Furthermore, ROS released from activated microglia via NOX2 was identified to couple microglial CR3-mediated iron accumulation and subsequent neuronal ferroptosis. Finally, supplementation with exogenous iron was found to recover the sensitivity of CR3^−/− mice to rotenone-induced neuronal ferroptosis. Altogether, our findings suggested that microglial CR3 regulates neuron ferroptosis through NOX2 -mediated iron accumulation in experimental Parkinsonism, providing novel points of the immunopathogenesis of neurological disorders.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103369"},"PeriodicalIF":10.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay of ROS, mitochondrial quality, and exercise in aging: Potential role of spatially discrete signaling","authors":"Siobhan M. Craige ,&nbsp;Rebecca K. Mammel ,&nbsp;Niloufar Amiri ,&nbsp;Orion S. Willoughby ,&nbsp;Joshua C. Drake","doi":"10.1016/j.redox.2024.103371","DOIUrl":"10.1016/j.redox.2024.103371","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103371"},"PeriodicalIF":10.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Over-activation of iNKT cells aggravate lung injury in bronchopulmonary dysplasia mice","authors":"Ming-Yan Wang ,&nbsp;Meng-Xu Yi ,&nbsp;Xing-Yu Mo ,&nbsp;Shan-Jie Wei ,&nbsp;Yu Qiao ,&nbsp;Zheng Zhang ,&nbsp;Zhao-Liang Su ,&nbsp;Hong-Yan Lu","doi":"10.1016/j.redox.2024.103370","DOIUrl":"10.1016/j.redox.2024.103370","url":null,"abstract":"<div><div>Bronchopulmonary dysplasia (BPD) is a severe lung disease in preterm infants, the abnormal proliferate and differentiate ability of type II epithelial cells (AEC II) is the key to the pathological basis of BPD. Mechanisms regarding abnormal AEC II in BPD remain unclear. The present work investigated the role and mechanisms of invariant natural killer T (iNKT) cells in lung disorder in BPD using public datasets, clinical samples, a hyperoxia-induced BPD mouse model and AEC II-iNKT cells transwell co-culture system. Firstly, we found that the NKT cells development factor IL-15 increased over time in patients with BPD in public databases, and clinically collected peripheral blood NKT cells in patients with BPD were increased. Subsequently, the percentage of iNKT cells increased in hyperoxia group compared with normoxia group, with the highest at P7, accompanied by increased activation with abnormal lung development. The administration of anti-CD1d neutralizing antibody to inhibit iNKT cells could alleviate the abnormal lung development of hyperoxia group mice, while α-GalCer administration could aggravate lung injury in hyperoxia group mice, and adoptive transfer of iNKT cells could aggravate the abnormal lung development in hyperoxia group mice. In addition, to further verify the role of iNKT cells on AEC II, AEC II-iNKT cells co-culture system was established. The presence of iNKT cells could aggravate the abnormal expression of SP-C and T1α under hyperoxia. Meanwhile, RNA-seq analysis showed that ferroptosis-related genes were highly expressed in AEC II co-cultured with iNKT cells under hyperoxia. We further validated the effect of the presence of iNKT cells under hyperoxia environment on AEC II ferroptosis levels, suggested that iNKT cells promote AEC II ferroptosis under hyperoxia, accompanied by decreased expression of SP-C and T1α. Our study found that the recruitment of iNKT cells in the lung may be an important cause of alveolarization disorder in BPD.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103370"},"PeriodicalIF":10.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the nexus of oxidative stress, ocular diseases, and small extracellular vesicles to identify novel glaucoma biomarkers through in-depth proteomics","authors":"Raquel Rejas-González ,&nbsp;Ana Montero-Calle ,&nbsp;Natalia Pastora Salvador ,&nbsp;María José Crespo Carballés ,&nbsp;Emma Ausín-González ,&nbsp;Juan Sánchez-Naves ,&nbsp;Sara Pardo Calderón ,&nbsp;Rodrigo Barderas ,&nbsp;Ana Guzman-Aranguez","doi":"10.1016/j.redox.2024.103368","DOIUrl":"10.1016/j.redox.2024.103368","url":null,"abstract":"<div><div>Chronic ocular pathologies such as cataracts and glaucoma are emerging as an important problem for public health due to the changes in lifestyle and longevity. These age-related ocular diseases are largely mediated by oxidative stress. Small extracellular vesicles (sEVs) are involved in cell-to-cell communication and transport. There is an increasing interest about the function of small extracellular vesicles (sEVs) in the eye. However, the proteome content and characterization of sEVs released by ocular cells under pathological conditions are not yet well known. Here, we aimed to analyze the protein profile of sEVs and the intracellular protein content from two ocular cell lines (lens epithelial cells and retinal ganglion cells) exposed to oxidative stress to identify altered proteins that could serve as potential diagnostic biomarkers. The protein content was analyzed by quantitative mass spectrometry-based proteomics. Validation was performed by WB and ELISA using cell extracts and aqueous humor from cataract and glaucoma patients. After data analysis, 176 and 7 dysregulated proteins with an expression ratio≥1.5 were identified in lens epithelial cells’ protein extract and sEVs, respectively, upon oxidative stress induction. In retinal ganglion cells, oxidative stress induction resulted in the dysregulation of 1033 proteins in cell extracts and 9 proteins in sEVs. In addition, by WB and ELISA, the dysregulation of proteins was mostly confirmed in aqueous humor samples from cataract or glaucoma patients in comparison to ICL individuals, with RAD23B showing high glaucoma diagnostic ability. Importantly, this work expands the knowledge of the proteome characterization of cataracts and glaucoma and provides new potential diagnostic glaucoma biomarkers.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103368"},"PeriodicalIF":10.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silibinin attenuates ferroptosis in acute kidney injury by targeting FTH1","authors":"Yijian Deng ,&nbsp;Liying Zeng ,&nbsp;Huaxi Liu ,&nbsp;Anna Zuo ,&nbsp;Jie Zhou ,&nbsp;Ying Yang ,&nbsp;Yanting You ,&nbsp;Xinghong Zhou ,&nbsp;Baizhao Peng ,&nbsp;Hanqi Lu ,&nbsp;Shuai Ji ,&nbsp;Ming Wang ,&nbsp;Yigui Lai ,&nbsp;Hiu Yee Kwan ,&nbsp;Xiaomin Sun ,&nbsp;Qi Wang ,&nbsp;Xiaoshan Zhao","doi":"10.1016/j.redox.2024.103360","DOIUrl":"10.1016/j.redox.2024.103360","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is primarily caused by renal ischemia-reperfusion injury (IRI), which is one of the most prevalent triggers. Currently, preventive and therapeutic measures remain limited. Ferroptosis plays a significant role in the pathophysiological process of IRI-induced AKI and is considered a key target for improving its outcomes. Silibinin, a polyphenolic flavonoid, possesses diverse pharmacological properties and is widely used as an effective therapeutic agent for liver diseases. Recent studies have reported that silibinin may improves kidney diseases, though the underlying mechanism remain unclear. In this study, we investigated whether silibinin protects against IRI-induced AKI and explored its mechanism of action. Our findings indicated that pretreatment with silibinin alleviated renal dysfunction, pathological damage, and inflammation in IRI-AKI mice. Furthermore, the results demonstrated that silibinin inhibited ferroptosis both <em>in vivo</em> and <em>in vitro</em>. Proteome microarrays were used to identify silibinin's target, and our results revealed that silibinin binds to FTH1. This binding affinity was confirmed through molecular docking, SPRi, CETSA, and DARTS. Additionally, co-IP assays demonstrated that silibinin disrupted the NCOA4-FTH1 interaction, inhibiting ferritinophagy. Finally, the inhibitory effects of silibinin on ferroptosis were reversed by knocking down FTH1 <em>in vitro</em>. In conclusion, our study shows that silibinin effectively alleviates AKI by targeting FTH1 to reduce ferroptosis, suggesting that silibinin could be developed as a potential therapeutic agent for managing and treating AKI.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103360"},"PeriodicalIF":10.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Interleukin-22 deficiency alleviates doxorubicin-induced oxidative stress and cardiac injury via the p38 MAPK/macrophage/Fizz3 axis in mice” [Redox Biol. 36 (2020) 101636]","authors":"Jing Ye ,&nbsp;Yuan Wang ,&nbsp;Yao Xu ,&nbsp;Zhen Wang ,&nbsp;Ling Liu ,&nbsp;Menglong Wang ,&nbsp;Di Ye ,&nbsp;Jishou Zhang ,&nbsp;Zicong Yang ,&nbsp;Yingzhong Lin ,&nbsp;Qingwei Ji ,&nbsp;Jun Wan","doi":"10.1016/j.redox.2024.103357","DOIUrl":"10.1016/j.redox.2024.103357","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"76 ","pages":"Article 103357"},"PeriodicalIF":10.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ALDH1A1 to enhance the efficacy of KRAS-targeted therapy through ferroptosis","authors":"Yunyi Bian ,&nbsp;Guangyao Shan ,&nbsp;Guoshu Bi ,&nbsp;Jiaqi Liang ,&nbsp;Zhengyang Hu ,&nbsp;Qihai Sui ,&nbsp;Haochun Shi ,&nbsp;Zhaolin Zheng ,&nbsp;Guangyu Yao ,&nbsp;Qun Wang ,&nbsp;Hong Fan ,&nbsp;Cheng Zhan","doi":"10.1016/j.redox.2024.103361","DOIUrl":"10.1016/j.redox.2024.103361","url":null,"abstract":"<div><div><em>KRAS</em> is among the most commonly mutated oncogenes in human malignancies. Although the advent of sotorasib and adagrasib, has lifted the “undruggable” stigma of <em>KRAS</em>, the resistance to KRAS inhibitors quickly becomes a major issue. Here, we reported that aldehyde dehydrogenase 1 family member A1 (ALDH1A1), an enzyme in retinoic acid biosynthesis and redox balance, increases in response to KRAS inhibitors and confers resistance in a range of cancer types. KRAS inhibitors' efficacy is significantly improved in sensitive or drug-resistant cells, patient-derived organoids (PDO), and xenograft models by <em>ALDH1A1</em> knockout, loss of enzyme function, or inhibitor. Furthermore, we discovered that ALDH1A1 suppresses the efficacy of KRAS inhibitors by counteracting ferroptosis. ALDH1A1 detoxicates deleterious aldehydes, boosts the synthesis of NADH and retinoic acid (RA), and improves RARA function. ALDH1A1 also activates the CREB1/GPX4 pathway, stimulates the production of lipid droplets in a pH-dependent manner, and subsequently prevents ferroptosis induced by KRAS inhibitors. Meanwhile, we established that GTF2I is dephosphorylated at S784 via ERK by KRAS inhibitors, which hinders its nuclear translocation and mediates ALDH1A1's upregulation in response to KRAS inhibitors. In summary, the results offer valuable insights into targeting ALDH1A1 to enhance the effectiveness of KRAS-targeted therapy through ferroptosis in cancer treatment.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103361"},"PeriodicalIF":10.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003392/pdfft?md5=10e678c6a7a97765ade0fbe6e40e7455&pid=1-s2.0-S2213231724003392-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione peroxidase 3 is essential for countering senescence in adipose remodelling by maintaining mitochondrial homeostasis","authors":"Yijie Song ,&nbsp;Mengjie Zhu ,&nbsp;Md Ariful Islam ,&nbsp;Wenyi Gu ,&nbsp;Kavsar Alim ,&nbsp;Chien-shan Cheng ,&nbsp;Jingxian Chen ,&nbsp;Yu Xu ,&nbsp;Hongxi Xu","doi":"10.1016/j.redox.2024.103365","DOIUrl":"10.1016/j.redox.2024.103365","url":null,"abstract":"<div><div>Adipose tissue senescence is a precursor to organismal aging and understanding adipose remodelling contributes to discovering novel anti-aging targets. Glutathione peroxidase 3 (GPx3), a critical endogenous antioxidant enzyme, is diminished in the subcutaneous adipose tissue (sWAT) with white adipose expansion. Based on the active role of the antioxidant system in counteracting aging, we investigated the involvement of GPx3 in adipose senescence. We determined that knockdown of GPx3 in adipose tissue by adeno-associated viruses impaired mitochondrial function in mice, increased susceptibility to obesity, and exacerbated adipose tissue senescence. Impairment of GPx3 may cause mitochondrial dysfunction through inner mitochondrial membrane disruption. Adipose reshaping management (cold stimulation and intermittent diet) counteracted the aging of tissues, with an increase in GPx3 expression. Overall metabolic improvement induced by cold stimulation was partially attenuated when GPx3 was depleted. GPx3 may be involved in adipose browning by interacting with UCP1, and GPx3 may be a limiting factor for intracellular reactive oxygen species (ROS) accumulation during stem cell browning. Collectively, these findings emphasise the importance of restoring the imbalanced redox state in adipose tissue to counteract aging and that GPx3 may be a potential target for maintaining mitochondrial homeostasis and longevity.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103365"},"PeriodicalIF":10.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724003434/pdfft?md5=649f28366f53f2b6e4459dfd707f9411&pid=1-s2.0-S2213231724003434-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}