The FASEB Journal最新文献

{"title":"Exploring Therapeutic Targets From Spreading Patterns Against Respiratory Syncytial Virus","authors":"Han Zhang,&nbsp;Zhao Zhang,&nbsp;Yixuan Yang,&nbsp;Jingjing Pei","doi":"10.1096/fj.202500509RR","DOIUrl":"https://doi.org/10.1096/fj.202500509RR","url":null,"abstract":"<p>Human respiratory syncytial virus (RSV) is a pathogen that causes severe respiratory illness in humans, primarily infecting infants, young children, the elderly, and adults with chronic health conditions. Each year, approximately 3.6 million children under the age of 5 are hospitalized worldwide, with over 100 000 fatalities reported. Currently, available RSV vaccines and antiviral drugs have several limitations, including inadequate immune persistence, limited applicability to specific populations, strict timing of treatment, and the risk of adverse reactions. RSV spreads through three main infection modes: syncytia formation, receptor-dependent infection of free viral particles, and transmission via actin filaments. These modes of transmission are key pathways that contribute to viral spread and pathogenicity while exposing potential targets for prevention and treatment. This is a complex process involving multiple aspects that remain not fully understood. Here, we review the mechanisms by which RSV infects and spreads within the host and explore the role of host factors in these processes, aiming to provide a theoretical and practical basis for identifying potential antiviral targets.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500509RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse Effects of Nicotinamide Mononucleotide Supplementation on Declining Quality of Oocytes With Polycystic Ovary Syndrome","authors":"Yong Fan,&nbsp;Qingyun Hu,&nbsp;Xun Wu,&nbsp;Peng Lang,&nbsp;Yi Wei,&nbsp;Runxin Yi,&nbsp;Chenwei He,&nbsp;Tangyi Geng,&nbsp;Chun Zhao,&nbsp;Shuai Zhou,&nbsp;Junqiang Zhang,&nbsp;Xiufeng Ling","doi":"10.1096/fj.202500921R","DOIUrl":"https://doi.org/10.1096/fj.202500921R","url":null,"abstract":"<p>Polycystic ovary syndrome (PCOS) adversely impacts oocyte quality, underscoring effective interventions as a central focus of research. Our study demonstrates that nicotinamide mononucleotide (NMN) not only restores NAD⁺ homeostasis in oocytes from PCOS mice but also enhances the developmental rate of PCOS oocytes during in vitro maturation (IVM). Transcriptomic analysis and experimental validation suggest that NMN helps reverse the decline in PCOS oocyte quality by mitigating oxidative stress, improving mitochondrial function, and preserving spindle morphology. Mechanistically, we found that NMN supplementation upregulates SIRT1 expression, which responds to fluctuations in NAD⁺ levels through the NAD⁺ salvage pathway regulated by nicotinamide mononucleotide adenylyltransferase (NMNAT). In conclusion, our findings highlight the potential of NMN in improving PCOS oocyte quality, offering valuable insights for clinical PCOS treatment and the advancement of assisted reproductive technology.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500921R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Senolytic Therapy Ameliorates Renal Fibrosis Post-Acute Kidney Injury by Alleviating Renal Senescence”","authors":"Jun Wang","doi":"10.1096/fj.202502421","DOIUrl":"https://doi.org/10.1096/fj.202502421","url":null,"abstract":"<p>Li, C., Shen, Y., Huang, L., Liu, C., and Wang, J. (2021), Senolytic therapy ameliorates renal fibrosis post-acute kidney injury by alleviating renal senescence. The FASEB Journal, 35:e21229. https://doi.org/10.1096/fj.202001855rr</p><p>The authors report errors in assembling the α-SMA images in Figure 5G, and Supplemental Figures S2F and S5A.</p><p>The same α-SMA immunohistochemical staining image was used for the sham group and DQ group in Figure 5G and the sham group in Figure S2F. The same α-SMA immunofluorescent staining image was used for both the TGF-β group and TGF-β+DQ group in Figure S5A.</p><p>We apologize for these errors. These mistakes do not affect the results and conclusions presented in this article.</p><p>The corrected Figure 5 and Supplemental Figures S2 and S5 are as follows:</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202502421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelogenin Null Mice Develop Osteoarthritis, While Its Application Mitigates Disease Phenotypes in a Rat Model","authors":"Omer Helwa-Shalom,&nbsp;Yarden Kahlon-Suki,&nbsp;Shany Ivon Markowitz,&nbsp;Koby Goren,&nbsp;Dekel Shilo,&nbsp;Shira Schoonmaker,&nbsp;Chen Yochanan,&nbsp;Yechiel N. Gellman,&nbsp;Shaul Beyth,&nbsp;Dan Deutsch,&nbsp;Anat Blumenfeld,&nbsp;Hani Nevo,&nbsp;Amir Haze","doi":"10.1096/fj.202500827R","DOIUrl":"https://doi.org/10.1096/fj.202500827R","url":null,"abstract":"<p>Previous studies have demonstrated that recombinant human amelogenin protein (rHAM⁺) promotes healing of injured articular cartilage, subchondral bone, and skeletal ligaments. Therefore, we speculated that amelogenin may play a role in osteoarthritis (OA) development. Aged amelogenin-null and wild-type mice underwent micro-computed tomography (micro-CT) and histological analyses to assess OA-related changes. Additionally, OA was induced in rat knees via destabilization of the medial meniscus, followed by treatment with 0.5 mg/mL rHAM⁺ dissolved in propylene glycol alginate (PGA) or PGA alone. Magnetic resonance imaging (MRI) and histological analyses were performed. Twenty-three-month-old amelogenin-null mice exhibited severe OA features, including cartilage loss, joint space narrowing, and osteophyte formation, whereas wild-type mice showed only mild, age-related changes. OA pathology was evident in 12-month-old amelogenin-null mice, by increased matrix metalloproteinase-13 (MMP-13) and decreased type II collagen expression. In osteoarthritic rats, MRI analyses demonstrated that treatment with rHAM⁺ delayed disease progression and improved OA phenotypes. Twenty-four weeks posttreatment, the levels of type II collagen increased, while MMP-13 and type X collagen decreased. MMP-13 reduction was detected as early as 2 weeks posttreatment, contributing to cartilage preservation. Furthermore, similar to the known effect of rHAM⁺ in acute injuries, recruitment of CD105-positive mesenchymal stem cells to the cartilage was detected 5 days posttreatment. Lack of amelogenin led to the development of osteoarthritic phenotypes, whereas in the induced osteoarthritis model, a single application of amelogenin inhibited joint deterioration and partially healed osteoarthritic damage compared with the control. These findings highlight the potential of amelogenin as a disease-modifying agent for OA.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500827R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of Skeletal Muscle Mitochondrial Glutamic-Oxaloacetic Transaminase (GOT2) Enhances Oxaloacetate Inhibition of Succinate Dehydrogenase and Alters Substrate Selectivity","authors":"Brian D. Fink,&nbsp;Ritu Som,&nbsp;Liping Yu,&nbsp;William I. Sivitz","doi":"10.1096/fj.202501071R","DOIUrl":"https://doi.org/10.1096/fj.202501071R","url":null,"abstract":"<p>Oxaloacetate (OAA) is converted to aspartate by mitochondrial glutamic-oxaloacetic transaminase 2 (GOT2) along with the conversion of glutamate to alpha-ketoglutarate (α-KG). Glutamate can also be directly converted to α-KG by glutamate dehydrogenase. In past work, we found that in skeletal muscle mitochondria energized by succinate alone, oxaloacetate accumulates and inhibits succinate dehydrogenase (complex II) in a manner dependent on inner membrane potential (ΔΨ). Here, we tested the hypothesis that deleting GOT2 would increase OAA concentrations, decrease complex II-energized respiration, and alter the selectivity of succinate versus glutamate for energy. Incubating wild-type mitochondria with succinate and glutamate revealed that increments in ADP increased OAA and caused a preferential use of glutamate for energy. Deletion of GOT2 compared to wild-type decreased complex II energized respiration, increased OAA, and decreased consumption of glutamate relative to succinate. OAA accumulation was also associated with decreased conversion of succinate to fumarate and malate. These findings are consistent with GOT2 control of metabolite flow through succinate dehydrogenase via regulation of OAA and consequent inhibition of succinate dehydrogenase. In contrast to respiration energized at complex II, when mitochondria were energized at complex I by pyruvate + malate, respiration did not differ between GOT2KO and WT mitochondria, and oxaloacetate was not detectable. In summary, GOT2 and OAA mediate complex II respiration and mitochondrial energy substrate selectivity.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501071R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NKp30: A Key Membrane Molecule in the Fight Against Cancer and Infection","authors":"Yushu Shao,&nbsp;Yang Zhang,&nbsp;Jiaying Cao,&nbsp;Junyu He,&nbsp;Qian He,&nbsp;Yan Lei,&nbsp;Ning Tang,&nbsp;Yanhong Zhou","doi":"10.1096/fj.202501490R","DOIUrl":"https://doi.org/10.1096/fj.202501490R","url":null,"abstract":"<p>Natural killer cells (NK) are crucial components of the immune system. NKp30, a significant activation receptor on the NK cell membrane, plays a cytotoxic role by recognizing and binding to corresponding ligands. This interaction mediates the activation of NK cells and the release of regulatory factors, participating in antitumor and anti-infection processes. This review systematically summarizes the structural features and basic functions of NKp30, the impact of N-terminal glycosylation on NKp30 function, related NKp30 ligands and their roles, as well as the antitumor and anti-infective functions and mechanisms of NKp30. The aim is to provide a new perspective for a comprehensive understanding of NKp30 function.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501490R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Level of a Short Form of Multidrug Resistance-Associated Protein 1 Is Elevated in Plasma Small Extracellular Vesicles Derived From Patients With Pancreatic Ductal Adenocarcinoma","authors":"Kritisha Bhandari,&nbsp;Madison Lu,&nbsp;Gillian Marshall,&nbsp;Jeng Shi Kong,&nbsp;Chao Xu,&nbsp;Ajay Jain,&nbsp;Ying Huang,&nbsp;Michael A. Hollingsworth,&nbsp;Wei-Qun Ding","doi":"10.1096/fj.202500874R","DOIUrl":"https://doi.org/10.1096/fj.202500874R","url":null,"abstract":"<div>\u0000 \u0000 <p>Multidrug resistance-associated protein 1 (MRP1) is an ATP-dependent transmembrane efflux pump that confers drug resistance. MRP1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and other malignancies. However, its diagnostic value in cancer has not been explored. The present study examined MRP1 expression in plasma small extracellular vesicles (sEVs) derived from PDAC and colon cancer patients. The human plasma samples were obtained from the NCI-sponsored Cooperative Human Tissue Network, Stephenson Cancer Center, and Oklahoma Blood Institute. sEVs were isolated using double filtration followed by the polymer precipitation method or using ultracentrifugation. Western blotting was performed to evaluate the expression level of MRP1, and proteomics were applied to confirm the detection of a short form of MRP1 in plasma sEVs. A short form of MRP1, representing the region between QCRL-1 and C-terminus domains of the protein, was identified in plasma sEVs, and its level was significantly elevated in plasma sEVs derived from patients with early- and late-stage PDAC, compared with matched healthy subjects (<i>n</i> = 34 for each group). The level of the short form of MRP1 was also elevated in plasma sEVs derived from patients with colon cancer (<i>n</i> = 44) but not in those derived from patients with breast cancer (<i>n</i> = 15). The levels of the short form of MRP1 in plasma sEVs were not related to the chemotherapy status of the patients. We thus conclude that a short form of MRP1 is identified in plasma sEVs and its expression level is significantly elevated in patients with early-stage and late-stage PDAC, irrespective of their treatment status.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disintegrin Rhodostomin Mutant Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy by Suppressing Both Integrin αvβ3 and α5β1","authors":"Yu-Chien Tsao,&nbsp;Shun-Hua Chen,&nbsp;Yi-Chun Ou,&nbsp;Woei-Jer Chuang,&nbsp;Chang-Hao Yang,&nbsp;Chia-Jhen Lin,&nbsp;Sheng-Min Hsu","doi":"10.1096/fj.202402498RR","DOIUrl":"https://doi.org/10.1096/fj.202402498RR","url":null,"abstract":"<div>\u0000 \u0000 <p>Proliferative vitreoretinopathy (PVR) is a severe complication after rhegmatogenous retinal detachment (RD) surgery and needs further surgical treatments. So far there are no effective drugs for prevention and treatment of PVR. Both integrins αvβ3 and α5β1 are related to human PVR formation. Disintegrins are antagonists of integrins. The drug, a mutant of snake venom-derived disintegrin, also called disintegrin Rhodostomin (Rho) mutant, is a potent antagonist of both integrins αvβ3 and α5β1, of which the effect on PVR remains poorly understood. In vitro assays were used to assess the effects of disintegrin Rho mutant treatment on the proliferation, migration, and adhesion of the retinal pigment epithelial (RPE) cell line derived from human, ARPE-19. In vivo, mice with PVR induction were treated with disintegrin Rho mutant and monitored for PVR severity. In vitro results showed that disintegrin Rho mutant reduced the migration, proliferation, and adhesion of ARPE-19 cells. In vivo results revealed that it could significantly ameliorate the severity of PVR and suppress expression of both integrin αvβ3 and α5β1 and epithelial-mesenchymal transition (EMT) in mouse eyes. Besides, we found decreases in Akt, STAT3, and ERK activation by disintegrin Rho mutant both in vitro and in vivo. In conclusion, disintegrin Rho mutant mitigates experimental PVR with reduced expression of both integrin αvβ3 and α5β1 and presents a potential therapeutic option for PVR in humans.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights Into Coat Color Variation: Unraveling the Role of ASIP by Gene Editing in Fine-Wool Sheep","authors":"Xue-mei Zhang,&nbsp;Mei-yu Qiu,&nbsp;Li Liao,&nbsp;Bing Han,&nbsp;Ya-di Deng,&nbsp;Ning Zhang,&nbsp;La-ti Hai,&nbsp;Long Liang,&nbsp;Ming-jun Liu","doi":"10.1096/fj.202500355R","DOIUrl":"https://doi.org/10.1096/fj.202500355R","url":null,"abstract":"<div>\u0000 \u0000 <p>Sheep coat color is an important phenotypic trait that influences consumer preferences and breeding. Although the <i>Agouti</i> Signaling Protein (<i>ASIP</i>) gene has been linked to pigmentation, the mechanisms underlying its function remain unclear. In a previous study, we generated <i>ASIP</i> gene-edited fine-wool sheep (F0) with diverse coat colors using CRISPR/Cas9. Building on this foundation, the present study investigates coat color variation in 33 F1 offspring produced by mating F0 gene-edited rams with either F0 gene-edited ewes or wild-type white ewes. Comprehensive genotyping identified two inherited <i>ASIP</i> mutations—a 4-bp deletion and a 27-bp deletion with a 1-bp insertion—alongside natural variants (D₅, D₉) and copy number variation. These genetic differences were associated with a wide range of coat color phenotypes in the F1 population. To explore the underlying mechanisms, we conducted histological analyses (H&amp;E staining), immunohistochemistry, melanin content quantification, qRT-PCR, and Western blotting. Results showed that dark-coated individuals exhibited reduced <i>ASIP</i> expression and elevated levels of <i>TYR</i> and <i>TYRP1</i>, consistent with increased eumelanin synthesis. In contrast, white-coated sheep showed higher <i>ASIP</i> expression and lower levels of melanogenic enzymes. Our findings provide functional validation that <i>ASIP</i> is a central regulator of pigmentation in sheep and reveal how the interplay between gene editing, natural mutations, and gene dosage contributes to diverse coat color outcomes. This work establishes a valuable model for dissecting coat color genetics and offers a molecular framework for future breeding strategies aimed at wool color diversification and economic trait improvement in fine-wool sheep.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aldehyde Oxidase 1 Deficiency Enhances Aerobic Exercise Performance by Promoting Skeletal Muscle Adaptation and Improving Mitochondrial Function","authors":"Yan Liu,&nbsp;Qi-Quan Wang,&nbsp;Tian-E. Huang,&nbsp;Meng Yao,&nbsp;Ben-Hui Wang,&nbsp;Chun-Ping Huang,&nbsp;Shu Wang,&nbsp;Yi-Fan Lu,&nbsp;Xin-Qiang Lan,&nbsp;Xiao-Li Tian,&nbsp;Yang Xiang","doi":"10.1096/fj.202500240R","DOIUrl":"https://doi.org/10.1096/fj.202500240R","url":null,"abstract":"<p>Aerobic exercise has significant health benefits, including preventing chronic diseases like sarcopenia. It strongly depends on muscle fiber types, with higher oxidative fiber ratios enhancing endurance. However, the molecular mechanisms underlying aerobic exercise capacity remain incompletely understood. In this study, we identified 395 genes associated with muscle fiber types, among which 39 were linked to metabolic pathways. Notably, we focused on aldehyde oxidase 1 (AOX1), a molybdenum flavin enzyme, due to its unique non-mitochondrial localization, suggesting a potential causal role in regulating muscle metabolism. We further revealed a significant downregulation of <i>Aox1</i> mRNA expression in the skeletal muscle of mice after two weeks of exercise training, indicating its involvement in exercise adaptation. To further explore this link, we generated <i>Aox1</i> knockout (KO) mice and subjected them to endurance capacity tests. <i>Aox1</i> KO mice exhibited significantly enhanced exercise endurance compared to wild-type (WT) controls, accompanied by a shift toward a more oxidative muscle phenotype, as indicated by an increased proportion of oxidative fibers. Mechanistically, <i>Aox1</i> KO mice exhibit increased expression of PGC-1α, enhanced mitochondrial function, and increased capillary density in skeletal muscle, facilitating improved oxygen delivery and utilization during exercise. Additionally, in vitro experiments using C2C12 myotubes revealed that <i>Aox1</i> knockdown alleviated starvation- and TNF-α-induced muscle atrophy, which partially mimics sarcopenia, highlighting its protective role against aging- and stress-induced muscle damage. These findings identify AOX1 as a negative regulator of aerobic exercise capacity and stress resilience, advancing our understanding of skeletal muscle adaptation and highlighting AOX1 as a potential target for improving exercise performance and mitigating sarcopenia.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500240R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}