Molecular and Cellular Biology最新文献

Deciphering the m6A Epitranscriptomic Landscape of mRNAs in Breast Cancer Cells. 解读乳腺癌细胞中mrna的m6A表转录组学景观。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-10-06 DOI: 10.1080/10985549.2025.2560956

Konstantina Athanasopoulou, Panagiotis G Adamopoulos, Panagiotis Tsiakanikas, Glykeria N Daneva, Ioannis Prassas, George M Yousef, Eleftherios P Diamandis, Andreas Scorilas

{"title":"Deciphering the m6A Epitranscriptomic Landscape of mRNAs in Breast Cancer Cells.","authors":"Konstantina Athanasopoulou, Panagiotis G Adamopoulos, Panagiotis Tsiakanikas, Glykeria N Daneva, Ioannis Prassas, George M Yousef, Eleftherios P Diamandis, Andreas Scorilas","doi":"10.1080/10985549.2025.2560956","DOIUrl":"https://doi.org/10.1080/10985549.2025.2560956","url":null,"abstract":"N6-methyladenosine (m6A), the most prevalent modification in mRNAs, influences mRNA stability, splicing, and translation. Dysregulation of m6A patterns has been linked to various diseases, including cancer, highlighting its significance in cellular homeostasis. However, accurate detection and precise quantification of m6A sites within individual transcripts remains challenging. In this study, we employed nanopore sequencing to achieve transcriptome-wide, base-resolution map of the m6A methylome in human breast cancer cells. By investigating m6A distribution across breast cancer cell lines and implementing a CRISPR/Cas9-based knockout of the major m6A eraser ALKBH5, we provide insights into the differential methylation levels and motif-specific characteristics of m6A transcriptomic sites. We elucidated the m6A epitranscriptome in five well-established breast cancer cell lines derived from distinct molecular subtypes of the disease and confirmed a DRACH-dependent activity of ALKBH5. Comparative methylation analysis with the non-cancerous MCF-10A cell line revealed that MCF-7 and BT-474 breast cancer cells are primarily hypomethylated, while BT-20, MDA-MB-231 and SK-BR-3 cells show widespread hypermethylation. These cell line-based patterns highlight the potential regulatory role of m6A in breast cancer heterogeneity. Overall, our findings enhance the understanding of m6A dynamics in breast cancer.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233033","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}

引用次数: 0

Effects of DNA Methylation Inhibitors on Molecular and Structural Changes in Chromatin Organization in Leukemia Cells. DNA甲基化抑制剂对白血病细胞染色质组织分子和结构变化的影响。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-29 DOI: 10.1080/10985549.2025.2560965

Przemysław Sareło, Aleksandra Kaczorowska, Marlena Gąsior-Głogowska, Kinga Godkowicz, Weronika Lamperska, Sławomir Drobczyński, Ewa Zioło, Anna Licznerska, Tomasz Wróbel, Halina Podbielska, Wojciech Kałas, Marta Kopaczyńska

{"title":"Effects of DNA Methylation Inhibitors on Molecular and Structural Changes in Chromatin Organization in Leukemia Cells.","authors":"Przemysław Sareło, Aleksandra Kaczorowska, Marlena Gąsior-Głogowska, Kinga Godkowicz, Weronika Lamperska, Sławomir Drobczyński, Ewa Zioło, Anna Licznerska, Tomasz Wróbel, Halina Podbielska, Wojciech Kałas, Marta Kopaczyńska","doi":"10.1080/10985549.2025.2560965","DOIUrl":"https://doi.org/10.1080/10985549.2025.2560965","url":null,"abstract":"DNA methylation inhibitors are widely used in treating myeloid malignancies, yet their precise effects on chromatin organization and nuclear architecture remain incompletely understood. Here, the integrated molecular, cellular, and biophysical approaches to investigate the impact of azacitidine (AZA) and decitabine (DEC) on chromatin structure and nuclear mechanics in AML-007 leukemia cells are presented. Confocal microscopy revealed drug-induced alterations in nuclear morphology and actin cytoskeleton organization, with DEC inducing significant nuclear enlargement and disorganization at lower concentrations (1.0 µM) compared to AZA (5.0 µM). Chromatin condensation assays demonstrated that DEC increased chromatin accessibility in a concentration-dependent manner, while AZA produced subtler effects. Optical tweezers measurements showed both agents reduced nuclear stiffness, with DEC exerting a greater impact. Spectroscopic analysis confirmed differential drug incorporation into DNA, with higher methylation loss and structural changes observed following DEC treatment. Refractive index mapping revealed chromatin decompaction, aligning with increased accessibility and nuclear softening. These findings demonstrate that DNA hypomethylating agents exert distinct, concentration-dependent effects on nuclear organization and chromatin structure, which can be quantified through molecular and biophysical readouts. This study underscores the value of integrative methods for revealing epigenetic drug effects on chromatin architecture in leukemia cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186297","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}

引用次数: 0

Loss of E-Cadherin Alters Cigarette Smoke Extract (CSE)-Induced Damage and Repair Responses in Human Airway Epithelial Cells; Implications for Chronic Obstructive Pulmonary Disease (COPD). e -钙粘蛋白的缺失改变了香烟烟雾提取物（CSE）诱导的人气道上皮细胞损伤和修复反应对慢性阻塞性肺疾病（COPD）的影响。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-29 DOI: 10.1080/10985549.2025.2560946

Xinzi Zheng, Kingsley Okechukwu Nwozor, Marnix Jonker, Marissa Wisman, Martijn C Nawijn, Irene H Heijink

{"title":"Loss of E-Cadherin Alters Cigarette Smoke Extract (CSE)-Induced Damage and Repair Responses in Human Airway Epithelial Cells; Implications for Chronic Obstructive Pulmonary Disease (COPD).","authors":"Xinzi Zheng, Kingsley Okechukwu Nwozor, Marnix Jonker, Marissa Wisman, Martijn C Nawijn, Irene H Heijink","doi":"10.1080/10985549.2025.2560946","DOIUrl":"https://doi.org/10.1080/10985549.2025.2560946","url":null,"abstract":"COPD is characterized by airway epithelial barrier dysfunction. We hypothesized that downregulation of E-cadherin results in abnormal responses to cigarette smoke extract (CSE) with impaired repair and increased pro-inflammatory activity. We used CRISPR-Cas9-engineered 16HBE cells with 1-2 copies of the CDH1 gene encoding E-cadherin (CDH1+/+ or CDH1+/-) to study effects on tight junctional protein zonula occludens (ZO-1), CSE-induced epithelial barrier dysfunction using electric cell-substrate impedance sensing and pro-inflammatory cytokine production. In airway epithelial cells (AECs) from nine COPD stage IV transplant lungs and tracheobronchial tissue of nine non-COPD donors, we assessed E-cadherin, ZO-1 and pro-inflammatory cytokines. Lower electrical resistance in CDH1+/- 16HBE cells was accompanied by ZO-1 delocalization. CSE exposure induced transient barrier dysfunction, from which CDH1+/- cells recovered more slowly than CDH1+/+ cells. Similarly, CDH1+/- cells showed a delayed repair response upon wounding, while gene expression and secretion of pro-inflammatory cytokines were higher in unexposed cells (CXCL8, IL-1α) and/or showed a stronger CSE-induced increase (IL-1α, GM-CSF). AECs from COPD patients displayed lower E-cadherin and TJP1 levels and higher CSE-induced IL1A expression compared to control. Downregulation of E-cadherin resulted in disrupted ZO-1 expression, aggravated CSE-induced barrier dysfunction, impaired recovery from injury and a more pro-inflammatory epithelial phenotype in 16HBE cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186260","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}

引用次数: 0

Site Specific and Orientation Dependent CTCF Binding Determines VDJ Recombination at Murine Tcrb Locus. 位点特异性和定向依赖性CTCF结合决定小鼠Tcrb位点的VDJ重组。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-18 DOI: 10.1080/10985549.2025.2553650

Monika Yadav, Samriddhi Sharma, S R Rajalekshmi, Nidhi Bhasin, Jeanne Yimdjo, Karl Pfeifer, Madhulika Srivastava

{"title":"Site Specific and Orientation Dependent CTCF Binding Determines VDJ Recombination at Murine Tcrb Locus.","authors":"Monika Yadav, Samriddhi Sharma, S R Rajalekshmi, Nidhi Bhasin, Jeanne Yimdjo, Karl Pfeifer, Madhulika Srivastava","doi":"10.1080/10985549.2025.2553650","DOIUrl":"https://doi.org/10.1080/10985549.2025.2553650","url":null,"abstract":"CTCF is a multifunctional protein that mediates long-range cis-DNA interactions in mammalian genomes. Chromatin architecture governs spatial and functional interactions of gene regulatory elements at various loci and is impacted by the ability of CTCF to restrict cohesin complex dependent chromatin extrusion. In addition, at antigen receptor loci, long-range interactions facilitate spatial proximity of gene segments for VDJ recombination that generates functional genes encoding immunoglobulins and T-cell receptors in developing lymphocytes. To investigate the role of CTCF in VDJ recombination, we mutated CTCF binding sites (CBS) of murine Tcrb locus. Our analysis revealed that CBS interspersed in the domain encompassing variable gene segments (Vb) are not redundant. They exhibit independent but additive effects on dynamic chromatin organization leading to distinct VDJ recombination profiles in CBS mutants depending on positions of mutated CBS relative to Vb segments. Further, inversion of a single CBS drastically altered the chromatin loop organization and VDJ recombination profile. Our results demonstrate the critical importance of chromatin extrusion for generation of chromatin loops for VDJ recombination and underscore its dynamic impediment by CTCF binding at specific points within Vb segment domain to be essential to diversify the usage of Vb segments for VDJ recombination at Tcrb locus.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081065","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}

引用次数: 0

Lactate as an Exercise Mimetic: Mitigating Disuse Atrophy and Improving Muscle Endurance in Aging SAMP8 Mice. 乳酸作为运动模拟物：减轻衰老SAMP8小鼠的废用性萎缩和提高肌肉耐力。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-17 DOI: 10.1080/10985549.2025.2551616

Zhen Qi, Xi Liu, Yifen Chen, Linglin Zhang, Longhe Yang, Caihua Huang, Donghai Lin

{"title":"Lactate as an Exercise Mimetic: Mitigating Disuse Atrophy and Improving Muscle Endurance in Aging SAMP8 Mice.","authors":"Zhen Qi, Xi Liu, Yifen Chen, Linglin Zhang, Longhe Yang, Caihua Huang, Donghai Lin","doi":"10.1080/10985549.2025.2551616","DOIUrl":"https://doi.org/10.1080/10985549.2025.2551616","url":null,"abstract":"Lactate, historically considered a metabolic byproduct, has emerged as a key regulator of muscle physiology and metabolism. This study explores its potential as an exercise mimetic to counteract disuse muscle atrophy (DMA) in aging skeletal muscle using a hindlimb suspension model in senescence-accelerated prone 8 (SAMP8) mice. The mice were divided into four groups: Control, lactate-treated control, hindlimb suspension, and hindlimb suspension with lactate intervention. Lactate administration preserved gastrocnemius muscle mass, restored muscle strength, and attenuated oxidative fiber atrophy. Electrophoretic and histological analyses showed increased MyHC I expression, indicating protection of oxidative fibers. Functional assessments revealed improved muscle endurance and contractile force, while metabolomic profiling identified changes in energy metabolism, amino acid metabolism, and protein synthesis pathways. Specifically, lactate improved impaired branched-chain amino acid metabolism, suggesting enhanced protein synthesis. In addition, lactate boosted Cori cycle activity, upregulated hepatic lactate transporters, and increased lactate dehydrogenase B activity, facilitating efficient lactate metabolism and gluconeogenesis. These results provide new insights into the role of lactate as a metabolic regulator and highlight its potential as a therapeutic intervention to combat exercise-induced muscle wasting and preserve muscle function in aging and immobilized individuals.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075818","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}

引用次数: 0

Histone Acetyltransferases Gcn5 and Esa1 Regulate Occupancy of RSC to Maintain Nucleosome-Depleted Regions and Promote RSC Recruitment to Coding Regions Genome-Wide in Saccharomyces cerevisiae. 在酿酒酵母中，组蛋白乙酰转移酶Gcn5和Esa1调节RSC的占用以维持核小体缺失区域，并促进RSC向全基因组编码区域的招募。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-17 DOI: 10.1080/10985549.2025.2555901

Emily Biernat, Mansi Verma, Matthew Werick, Uzair Khan, Sama Joseph, Chhabi K Govind

{"title":"Histone Acetyltransferases Gcn5 and Esa1 Regulate Occupancy of RSC to Maintain Nucleosome-Depleted Regions and Promote RSC Recruitment to Coding Regions Genome-Wide in Saccharomyces cerevisiae.","authors":"Emily Biernat, Mansi Verma, Matthew Werick, Uzair Khan, Sama Joseph, Chhabi K Govind","doi":"10.1080/10985549.2025.2555901","DOIUrl":"https://doi.org/10.1080/10985549.2025.2555901","url":null,"abstract":"Chromatin remodelers are important for maintaining chromatin structure and regulating gene expression. In this study, we investigated the roles of histone acetyltransferases (HATs) Gcn5 and Esa1 in regulating RSC and histone occupancy on chromatin, as well as their impact on transcription across the genome. Our findings reveal distinct effects of HATs on RSC occupancy in promoters and ORFs. The lack of HATs leads to the accumulation of RSC, and it was greater in nucleosome-depleted regions (NDRs) containing fragile nucleosomes (FNs), relative to other NDRs. The increased RSC NDR-binding was greater in Esa1-deficient cells than in those lacking Gcn5. The increased RSC binding was not seen in cells lacking the H3 or H4 tails. The mutants also led to significant increases in histone occupancies around the NDRs genome-wide. Overall, the data suggest that hypoacetylated tails may recruit RSC to NDRs, especially to FN-containing NDRs, and that subsequent histone acetylation enhances histone eviction. The HAT mutants also exhibited reduced recruitment of TBP and Pol II. In contrast to the promoters, RSC occupancies were significantly reduced in transcribed ORFs in the HAT mutants. Thus, our data implicate HATs and RSC in maintaining NDRs, regulating chromatin structure, and promoting transcription.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-23"},"PeriodicalIF":2.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075791","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}

引用次数: 0

PARP1-Dependent and Independent Pathways for Resolution of Trapped Topoisomerase I Covalent Complexes. 捕获拓扑异构酶I共价复合物分解的parp1依赖和独立途径。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-16 DOI: 10.1080/10985549.2025.2555891

Benu Brata Das, Banhi Chowdhury, Sarita Das, Asmit Banerjee

{"title":"PARP1-Dependent and Independent Pathways for Resolution of Trapped Topoisomerase I Covalent Complexes.","authors":"Benu Brata Das, Banhi Chowdhury, Sarita Das, Asmit Banerjee","doi":"10.1080/10985549.2025.2555891","DOIUrl":"https://doi.org/10.1080/10985549.2025.2555891","url":null,"abstract":"Topoisomerase I (Top1) alleviates DNA supercoiling during replication and transcription, but its catalytic cycle can be hijacked by chemotherapeutic agents such as camptothecin (CPT), stabilizing Top1-DNA covalent complexes (Top1cc) that threaten genome integrity. Efficient resolution of these trapped intermediates is crucial to prevent replication stress, DNA breaks, and cell death. Poly (ADP-ribose) polymerase 1 (PARP1) is a key sensor of Top1cc, facilitating repair by recruiting tyrosyl-DNA phosphodiesterase 1 (TDP1) and modifying chromatin to promote lesion accessibility. Beyond this canonical pathway, emerging evidence highlights PARP1-independent mechanisms such as endo nucleolytic cleavage, proteolytic degradation of Top1 and replication-associated processing. Intriguingly, PARP1 appears to act as a molecular switch between TDP1 and the endonuclease pathway for the repair of Top1cc. This review highlights mechanisms of PARP1-dependent and -independent Top1cc repair pathways, their interplay and redundancy, and how their targeting can enhance Top1-based cancer therapies and overcome resistance.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-20"},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069991","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}

引用次数: 0

Acyl-CoA Reductase Far1 Deficiency Impairs Ether Lipid Production and Hypomyelination in Mouse Brains. 酰基辅酶a还原酶Far1缺乏损害小鼠脑内乙醚脂质生成和低髓鞘形成。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-11 DOI: 10.1080/10985549.2025.2548234

Tenga Takahashi, Kento Otsuka, Takayuki Sassa, Akio Kihara

{"title":"Acyl-CoA Reductase Far1 Deficiency Impairs Ether Lipid Production and Hypomyelination in Mouse Brains.","authors":"Tenga Takahashi, Kento Otsuka, Takayuki Sassa, Akio Kihara","doi":"10.1080/10985549.2025.2548234","DOIUrl":"https://doi.org/10.1080/10985549.2025.2548234","url":null,"abstract":"Mammalian cell membranes contain ether lipids, which include an alkyl chain derived from a fatty alcohol that is produced by fatty acyl-CoA reductases (FARs). There are two mammalian FAR genes, FAR1 and FAR2, and mutations in FAR1 cause the peroxisomal fatty acyl-CoA reductase 1 disorder (PFCRD), which is accompanied by various symptoms, including neurological disorders. To date, the contributions of FAR1 and FAR2 to brain ether lipid production and the molecular mechanism of PFCRD have remained unknown. To investigate these, we analyzed knockout (KO) mice of Far1 and Far2. In the brain, the expression levels of Far1 were higher than those of Far2, and Far1 was widely expressed. Lipidomic analyses showed that the quantity of ether lipids ethanolamine-plasmalogens was reduced in Far1 KO mice, with a complementary increase in diacyl-type phosphatidylethanolamines, but not in Far2 KO mice. Electron microscope analysis of the corpus callosum revealed reductions in the percentage of myelinated axons and myelin thickness in Far1 KO mice relative to WT mice. In conclusion, FAR1 is the major FAR isozyme involved in ether lipid synthesis in the brain, and its deficiency causes hypomyelination. We speculate that this hypomyelination is one of the causes of the neurological symptoms of PFCRD.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-16"},"PeriodicalIF":2.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033738","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}

引用次数: 0

Molecular Insights into the Pathophysiology of Dysregulated Erythropoiesis: The Crucial Role of Iron Homeostasis. 红细胞生成异常病理生理的分子洞察：铁稳态的关键作用。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-10 DOI: 10.1080/10985549.2025.2553648

Tohru Fujiwara, Hideo Harigae

{"title":"Molecular Insights into the Pathophysiology of Dysregulated Erythropoiesis: The Crucial Role of Iron Homeostasis.","authors":"Tohru Fujiwara, Hideo Harigae","doi":"10.1080/10985549.2025.2553648","DOIUrl":"https://doi.org/10.1080/10985549.2025.2553648","url":null,"abstract":"Erythropoiesis, i.e., process of red blood cell (RBC) production, is highly dependent on iron, with 60-70% of the total body iron incorporated into hemoglobin. Iron homeostasis is tightly regulated, given that both iron overload and deficiency can impair RBC development and function. Iron-loading anemias, such as sideroblastic anemia and thalassemia, are associated with ineffective erythropoiesis and systemic iron overload. Recent studies also highlight the role of ferroptosis, i.e., iron-dependent cell death, in erythroid failure under conditions of iron overload. Transcriptional repressor BTB and CNC homology 1 (BACH1), which is regulated by intracellular heme, is a potential key mediator of ferroptosis. In iron deficiency, limited iron availability impairs heme and globin biosynthesis, mitochondrial function, and erythropoietin responsiveness, while also inducing widespread changes in gene expression through DNA methylation, all of which contribute to dysregulated erythropoiesis. Under iron deficiency, BACH1 plays a critical role in maintaining the balance between heme and globin by suppressing globin gene expression, thereby preventing the aggregation of toxic non-heme globin. This review summarizes the current understanding of the mechanisms by which iron imbalance contributes to erythropoietic failure and highlights BACH1 as a potential integrative regulator in the pathophysiology of anemia in both iron-overload and iron-deficient states.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030057","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}

引用次数: 0

Immune Regulation of Itaconate and Its Derivatives in Liver Diseases. 衣康酸及其衍生物在肝脏疾病中的免疫调节作用。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-09-10 DOI: 10.1080/10985549.2025.2553660

Tianning Ge, Yifei Zhang

{"title":"Immune Regulation of Itaconate and Its Derivatives in Liver Diseases.","authors":"Tianning Ge, Yifei Zhang","doi":"10.1080/10985549.2025.2553660","DOIUrl":"https://doi.org/10.1080/10985549.2025.2553660","url":null,"abstract":"Over the past few decades, liver disease has emerged as one of the leading causes of death worldwide. Liver injury is frequently associated with infections, alcohol consumption, or obesity, which trigger hepatic inflammation and ultimately lead to progressive fibrosis and carcinoma. Although various cell populations contribute to inflammatory and fibrogenic processes in the liver, macrophages serve as a pivotal mediator. Hepatic macrophages exhibit substantial heterogeneity and perform diverse functions that depend on the pathological microenvironment. The immune response gene 1 (IRG1), a critical metabolic regulatory gene, encodes the mitochondrial enzyme aconitate decarboxylase 1 (ACOD1), which influences macrophage functional polarization by promoting the synthesis of itaconate, a metabolite produced via a side pathway of the tricarboxylic acid (TCA) cycle. Increasing evidence indicates that itaconate and its derivatives exert immunomodulatory effects in processes such as oxidative stress, viral infection, inflammation, tumorigenesis, and wound healing, thereby demonstrating significant potential for treating liver disorders. In this review, we summarize the roles of itaconate and its derivatives in liver diseases and their underlying mechanisms, thereby providing insights into the therapeutic potential of targeting macrophages.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030063","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}

引用次数: 0