The FASEB Journal最新文献

{"title":"Stem Cell Membrane Biomimetic Nano-Formulation Achieves the Delivery of MKP5 to Ameliorate Diabetic Kidney Disease via the P38 and ERK Pathway","authors":"Dandan Sun,&nbsp;Jianan Zhao,&nbsp;Yongjun Ma,&nbsp;Xinzhe Dong,&nbsp;Yafei Tian,&nbsp;Mingming Li,&nbsp;Xiangfeng Meng,&nbsp;Miao Wang,&nbsp;Shenhe Liu,&nbsp;Wei Wang,&nbsp;Ping Jiao,&nbsp;Jie Ma","doi":"10.1096/fj.202501936R","DOIUrl":"10.1096/fj.202501936R","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic kidney disease (DKD) is a complication of diabetes that frequently progresses to end-stage renal disease, posing a significant threat to patients' lives. Due to the complex microenvironment associated with DKD, current treatment and reversal strategies remain inadequate. While the protective role of mitogen-activated protein kinase phosphatase 5 (MKP5) in diabetes has been established, its specific function in DKD remains unclear. This study aims to investigate the role and underlying mechanism of MKP5 in DKD and propose a novel therapeutic target for its treatment. We found that MKP5 expression was reduced in the renal glomeruli of streptozotocin-induced DKD mice. MKP5-knockout mice exhibited more pronounced progression of DKD. The regulatory mechanism of MKP5 primarily involved modulation of the extracellular signal-regulated kinase (ERK) and P38 pathways in glomerular mesangial cells and podocytes, respectively. Consequently, polylactic acid-glycolic acid copolymer (PLGA) particles were employed to carry the MKP5 plasmid, with mesenchymal stem cell membrane (MSCM, M) serving as the external encapsulating structure, resulting in the fabrication of a nano-formulation designated MKP5@NP-M. This formulation inhibited the secretion of inflammatory factors in the glomerulus, prevented collagen deposition and mesangial expansion, thereby inhibiting the progression of DKD. These findings uncover the potential anti-inflammatory regulatory function of MKP5 in the glomerulus and provide a combined strategy for treating DKD.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058057","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":"ATP-Driven Allosteric Regulation of 14-3-3: Positive Modulation of ATP Hydrolysis and Negative Regulation of Peptide Binding","authors":"Priyanka Bagdiya,&nbsp;Neelesh Soni,&nbsp;Damini Jaiswal,&nbsp;Somavally Dalvi,&nbsp;Tejashree Kanitkar,&nbsp;M. S. Madhusudhan,&nbsp;Prasanna Venkatraman","doi":"10.1096/fj.202500445R","DOIUrl":"10.1096/fj.202500445R","url":null,"abstract":"<p>Many 14-3-3 paralogs, except sigma, could bind and hydrolyze ATP. However, the catalytic residues and the significance of ATP binding or hydrolysis remain unknown. Here we confirm that there are two binding pockets for ATP, one at the peptide binding amphipathic pocket and the other at the dimer interface. As predicted by a new computational method, CLICK, and by limited proteolysis coupled to mass spectroscopy, we identify E131 and E180 as the catalytic residues. We further confirm that ATP hydrolysis is an inherent property of 14-3-3, and mutations result in either gain or loss of ATPase activity. The dimeric fold of the protein is mandatory for ATP hydrolysis but not for peptide binding. While ATP at the dimer interface acts as an allosteric activator of ATP hydrolysis, it acts as a selective negative regulator of a nonphosphopeptide, originating from ExoS, a pathogenic Pseudomonas protein. This study for the first time, unveils the hidden allosteric properties of the 14-3-3 proteins and its role in excluding specific ligands of disease relevance.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500445R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038336","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":"Single Cell Geometry Regulates Self-Renewal Factors in Osteosarcoma Cells via WDR5 Dependent Chromatin Methylation","authors":"Ran Yan,&nbsp;Shengnan Gong,&nbsp;Lu Yang,&nbsp;Yixi Zhang,&nbsp;Wei Yan,&nbsp;Hao Wu,&nbsp;Tingting Li,&nbsp;Xiang Qin,&nbsp;Chunhui Wu,&nbsp;Shun Li,&nbsp;Yiyao Liu","doi":"10.1096/fj.202403381RR","DOIUrl":"10.1096/fj.202403381RR","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteosarcoma (OS) is the most common primary malignant bone tumor in juveniles and young adults. OS cells respond to the complex mechanical cues in the tumor microenvironment to adapt and remodel their phenotype and behaviors. The transformation of cell morphological characteristics is the first visual representation of cell response to mechanical signals. But the biomechanical mechanisms by which cellular geometry leads to the changes in OS cell behaviors remain unclear. Here, we used micropattern printing to generate square, round, and rectangular single-cell geometries of equal area to investigate the effects induced by cellular geometric morphologies of human osteosarcoma U-2 OS cells. We showed that, compared to square-shaped cells, U-2 OS cells confined to round and rectangular micropatterns had increased MLCK expression, which enhanced cytoskeletal contractility through myosin II phosphorylation. Increased cytoskeletal contractility promoted nuclear translocation of WDR5, which increased H3K4me3 and upregulated the expression of the self-renewal markers of Nanog, Oct4, and Sox2. Ultimately, the self-renewal capability of U-2 OS cells enhanced. Our study provides insights into nuclear mechanotransduction of OS cells by demonstrating that spatial confinement induced remodeling of single-cell geometry enhances self-renewal and stemness maintenance of OS cells through WDR5-dependent chromatin methylation, which may provide a new perspective for tumor mechanical medicine.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038337","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":"CD8+ T-Cell Deletion Suppressed the Development of Injury-Induced Experimental Neointimal Hyperplasia in Mice With or Without Chronic Stress","authors":"Jingyuan Jin,&nbsp;Meiling Piao,&nbsp;Xianji Piao,&nbsp;Shangzhi Shu,&nbsp;Longguo Zhao,&nbsp;Zhibo Wang,&nbsp;Xueling Yue,&nbsp;Jinshun Piao,&nbsp;Xianglan Jin,&nbsp;Lina Hu,&nbsp;Yongshan Nan,&nbsp;Xian Wu Cheng","doi":"10.1096/fj.202502380R","DOIUrl":"10.1096/fj.202502380R","url":null,"abstract":"<p>Chronic stress exacerbates cardiovascular injury and remodeling. Given the pivotal roles that cytotoxic CD8⁺ T cells play in pathobiology, we investigated potential role(s) of CD8⁺ T cells in stress-related vascular remodeling in a mouse carotid injury model. Eight-week-old male wild-type (CD8a^+/+) and CD8a knockout (CD8a^−/−) mice underwent carotid artery ligation plus cuff placement (L + C) with or without being subjected to chronic stress. At surgery conducted 2 weeks later, L + C alone had significantly promoted carotid neointimal hyperplasia and induced an extensive infiltration of CD8⁺ T cells into injured vascular tissues. Chronic stress further exacerbated neointimal formation and CD8⁺ T-cell infiltration. Genetically deleting CD8⁺ T cells significantly attenuated neointimal hyperplasia, collagen deposition, and proliferative PCNA-positive cells and reduced CD68-positive macrophage infiltration, the expressions of inflammatory genes (AT1R, galectin-3, MCP-1, VCAM-1, ICAM-1) and extracellular matrix-remodeling enzyme genes (MMP-2, MMP-9, cathepsin S, cathepsin K), and proliferative signaling-pathway proteins (p-Akt, p-p38, p-mTOR). Data from interferon (IFN)-γ knockout (IFN-γ^−/−) mice administered an IFN-γ-neutralizing antibody or an adoptive transfer of CD8⁺ T cells from IFN-γ^+/+ mice or IFN-γ^−/− mice further confirmed the CD8⁺ T-cell deletion-mediated protective effects against experimental neointimal hyperplasia in response to stress and injury. In vitro vascular smooth muscle cell experiments revealed that the cell migration and invasion abilities and mTOR/Akt signaling were sensitive to 5% stress serum from CD8a^+/+ mice. CD8⁺ T-cell deletion thus appears to ameliorate vascular remodeling, suggesting that genetic CD8⁺ T-cell modification might be a promising therapeutic target for managing proliferative vascular diseases in animals under chronic stress conditions.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202502380R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034629","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 “MCOLN1-Mediated Endoplasmic Reticulum Stress Induces Autophagy to Facilitate Lung Cancer Growth, Migration, and Invasion”","authors":"","doi":"10.1096/fj.202503235","DOIUrl":"10.1096/fj.202503235","url":null,"abstract":"<p>\u0000 <span>H. Jiang</span>, <span>X. Zhang</span>, <span>J. Cai</span>, <span>L. Li</span>, <span>P. Huang</span> and <span>S. Zhang</span> <span>MCOLN1-Mediated Endoplasmic Reticulum Stress Induces Autophagy to Facilitate Lung Cancer Growth, Migration, and Invasion</span>, <i>The FASEB Journal</i> <span>39</span><span>16</span> (<span>2025</span>) e70942, https://doi.org/10.1096/fj.202500930R\u0000 </p><p>In Section 2.4 | qPCR Detection, the text “GAPDH was taken as a reference gene, with the relative mRNA expression levels calculated by using the 2^-ΔΔCt2^−ΔΔCt method” was incorrect.</p><p>This should have read: “GAPDH was taken as a reference gene, with the relative mRNA expression levels calculated by using the 2^-ΔΔCt method.”</p><p>We apologize for this error.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202503235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021969","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":"Role of Inflammatory Cytokine Adsorption on VA-ECMO-Induced Acute Kidney Injury of Rats","authors":"Zihan Kou,&nbsp;Mengjun Ji,&nbsp;Qianlong Xue,&nbsp;Linlin Li,&nbsp;Ziquan Liu,&nbsp;Yingyi Zhang,&nbsp;Shike Hou,&nbsp;Xiangyan Meng,&nbsp;Haojun Fan","doi":"10.1096/fj.202500979R","DOIUrl":"10.1096/fj.202500979R","url":null,"abstract":"<div>\u0000 \u0000 <p>Extracorporeal membrane oxygenation (ECMO) is a high-risk, invasive therapy that sustains life through an external system. However, it often leads to complications such as bleeding, thrombosis, infection, and acute kidney injury (AKI). While up to 70% of ECMO patients develop AKI, the mechanisms driving this injury remain unclear, and effective treatments are limited. To address this, we developed a rat model of AKI induced by veno-arterial ECMO (VA-ECMO) and tested the protective effects of a multi-targeted inflammatory factor adsorption technology. Rats undergoing 3-h VA-ECMO exhibited hallmark renal dysfunction, including elevated levels of serum creatinine (Scr) and increased blood urea nitrogen (BUN), accompanied by upregulated renal inflammatory cytokines and tubular apoptosis. Incorporating a cytokine-targeted hemoperfusion device normalized Scr/BUN levels, reduced histopathological damage, and suppressed apoptosis. Mechanistically, adsorption therapy downregulated pro-inflammatory mediators and rebalanced apoptotic regulators, favoring anti-apoptotic Bcl-2 over pro-apoptotic Bax and cleaved caspase-3. These results demonstrate that cytokine adsorption alleviates VA-ECMO-induced AKI through dual suppression of systemic inflammation and intrinsic apoptosis. This study provides a mechanistic basis for clinical translation of adsorption-based strategies to preserve renal function in ECMO patients, addressing a critical unmet need in critical care.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034658","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":"Quality of Multidisciplinary Team Management in Healthcare-Associated Infection Prevention and Control and Its Impact on Multidrug-Resistant Organism Infections","authors":"Huihao Chen,&nbsp;Qijun Mo,&nbsp;Min Li,&nbsp;Yali Ding,&nbsp;Fengmei Guo,&nbsp;Fanxiang Chen","doi":"10.1096/fj.202500223RR","DOIUrl":"10.1096/fj.202500223RR","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to evaluate the quality of multidisciplinary team (MDT) management in healthcare-associated infection (HAI) prevention and control, as well as its impact on multidrug-resistant organism (MDRO) infections. This was a retrospective, single-center study with a small sample size. A total of 400 patients admitted to the Departments of Critical Care Medicine or Orthopedics between January 2022 and December 2023 were divided into a control group (<i>n</i> = 200, receiving conventional HAI management) and an experimental group (<i>n</i> = 200, undergoing MDT management). Key outcomes included compliance with infection prevention measures (e.g., isolation signs, disinfection preparation, and dedicated item use), infection control results (e.g., hand hygiene, appropriate antibiotic use, and medical waste disposal), and HAI incidence rates (e.g., MDRO, urinary, pulmonary, bloodstream, and skin infections). Pathogen specimen submission and satisfaction scores were also analyzed. The experimental group demonstrated higher implementation rates of infection prevention and control measures, and better adherence to hand hygiene, disinfection and isolation, appropriate antibiotic usage, dedicated use of medical items, and medical waste disposal, compared to the control group (<i>p</i> &lt; 0.05). MDRO and other infection rates were lower in the experimental group versus the control group (<i>p</i> &lt; 0.05). Furthermore, the experimental group showed higher pathogen specimen submission and qualified submission rates and a lower infection rate before antibiotic use compared to the control group (<i>p</i> &lt; 0.05). Healthcare workers in the experimental group reported greater safety awareness, awareness of HAI prevention and control, environmental management quality, and nursing service quality. Patients also expressed higher satisfaction with HAI management at discharge (<i>p</i> &lt; 0.05). MDT-based management enhances the quality of HAI prevention and control, effectively reducing MDRO infection rates and improving healthcare outcomes. However, the relatively small sample size from a single center may limit the generalizability of the findings.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034632","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":"Bio-Scaffold Developed With Decellularized Human Amniotic Membrane Composite 3D Umbilical Cord Mesenchymal Stem Cell Spheroids Accelerate the Repair of Rat Defective Wounds","authors":"Xianrui Wu,&nbsp;Chuwang Wang,&nbsp;Zheng Chen,&nbsp;Zhigang Xue,&nbsp;Jiadong Zhong,&nbsp;Wancong Zhang,&nbsp;Shijie Tang,&nbsp;Xiao Fu,&nbsp;Ping Li,&nbsp;Jianda Zhou","doi":"10.1096/fj.202500630RR","DOIUrl":"10.1096/fj.202500630RR","url":null,"abstract":"<div>\u0000 \u0000 <p>Defective wounds pose health risks, and treatment is challenging. Umbilical cord-derived mesenchymal stem cells (UCMSCs) show promise for healing. Primary UCMSCs were isolated and extracted in vitro, and the proliferation and differentiation characteristics were detected by flow cytometry and trilineage differentiation, and a 3D spherical cell culture was performed. The human amniotic membranes (HAMs) were decellularized, and two-dimensional suspension cells and 3D spheroids were compounded onto the decellularized HAMs (dHAMs) to make biological dressings, and the cytocompatibility of the bio-scaffold was detected in vitro. A rat model evaluated wound healing with 3D-UCMSCs-dHAM, measuring changes and conducting biopsies. 3D-UCMSCs can be tightly attached to the basal layer of dHAMs and form protein adhesions with fiber scaffolds to create good biological dressings. In rat animal experiments, histopathological examination confirmed that the healing quality of the biological dressing treatment group was higher; infiltrating fibroblasts were present in the dermis, neovascularization occurred, inflammatory infiltration was reduced, myofibroblast proliferation was reduced, collagen matrix production was reduced, and epidermal regeneration was complete. The biological dressing of 3D-UCMSCs-dHAM on the full-thickness defect wound of rats accelerates the remodeling and maturation of tissues, promotes the generation of neovascularization and the regeneration of skin attachments, and provides a new way for the treatment of 3D-UCMSCs in skin wounds in the future.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021970","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":"Organ-Specific Shifts in Aerobic and Anaerobic Metabolism Throughout Metamorphosis Into Adulthood in a Fully Aquatic Amphibian","authors":"Neal J. Dawson,&nbsp;Miguel Hernandez-Gonzalez,&nbsp;Pat Monaghan,&nbsp;Neil B. Metcalfe,&nbsp;Pablo Burraco","doi":"10.1096/fj.202502054R","DOIUrl":"10.1096/fj.202502054R","url":null,"abstract":"<p>Most animals experience abrupt developmental transitions involving major tissue remodeling, but the links with metabolic changes remain poorly understood. We examined ontogenetic changes in mitochondrial volume, oxidative capacity, oxygen consumption capacity, and anaerobic capacity across four organs (gut, liver, heart, and hindlimb muscle) in <i>Xenopus laevis</i> from metamorphosis to adulthood. These organs differ in the extent of developmental transformation. Mitochondrial volume increased notably in the metamorphosing gut and remained stable in the heart, decreased in the liver, and increased in the hindlimb muscle post-metamorphosis. Oxidative capacity was lower at metamorphosis than in later stages in the gut, heart, and hindlimb and showed the opposite pattern in the liver. Oxygen consumption capacity remained stable in the gut and liver but increased in the post-metamorphic heart and hindlimb. Anaerobic capacity increased with age across all organs. These findings reveal organ-specific patterns in metabolic capacity during development, reflecting varying energetic demands such as tissue remodeling during metamorphosis (e.g., in the gut) or increased locomotion post-metamorphosis (e.g., the heart and hindlimb muscle). Higher anaerobic capacity suggests an alternative way to cope with low oxygen during intense activity post-metamorphosis. This work provides a foundation for understanding how metabolic dynamics shape developmental transitions and their eco-evolutionary implications.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202502054R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034622","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":"Abundance of Maternal Mitochondrial Genome Is Dispensable up to the Mitochondrial Genome Activation in Post-Implantation Embryos","authors":"Miki Shavit,&nbsp;Marie Vancová,&nbsp;Jan Jedlicka,&nbsp;Tomáš Bílý,&nbsp;Mushrek Mahrouk,&nbsp;Jan Cendelin,&nbsp;Kateřina Grygarova,&nbsp;Kristýna Popelková,&nbsp;Zdeněk Tůma,&nbsp;Gabriela Pribanova,&nbsp;Jitka Kuncová,&nbsp;Jan Nevoral","doi":"10.1096/fj.202501179R","DOIUrl":"10.1096/fj.202501179R","url":null,"abstract":"<p>Mitochondria in the egg are suggested to be crucial for the onset of new life. However, there is ambiguous knowledge about the necessity for fertilization and early embryonic development. Therefore, we created a conditional <i>Tfam</i> knockout (<i>Tfam</i>^loxP/loxP; Zp3-Cre) to produce <i>Tfam</i>^null oocytes for investigation of the mitochondrial abundance in oocytes and early embryos. This created mtDNA-depleted eggs, although the abundance of mitochondria did not change. Despite decreased mitochondrial membrane potential, <i>Tfam</i>^null oocytes matured and were fertilized, which led to embryo formation. These <i>Tfam</i>^null eggs were developed into mtDNA-deficient blastocysts. Both TFAM and mtDNA appear to be dispensable for the success of embryo implantation. <i>Tfam</i> expression and mtDNA replication rescue the mtDNA-deficient embryo after implantation, enabling passage through a post-implantation bottleneck, and allowing survivor embryos to develop into healthy individuals. Our findings highlight the uncoupled relationship between mtDNA replication and mitochondrial abundance in the growing oocyte and show the importance of the oocyte bulk mtDNA for successful mitochondrial activation in post-implantation embryos.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501179R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012647","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}