Microbial Cell最新文献

Organelle activity organized by the endoplasmic reticulum-mitochondria encounter structure -ERMES- is essential for Podospora anserina development. 由内质网-线粒体相遇结构（ermes）组织的细胞器活动对鹅足孢的发育至关重要。

IF 3.9 3区生物学

Microbial Cell Pub Date : 2025-09-12 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.09.860

Melisa Álvarez-Sánchez, Matías Ramírez-Noguez, Beatriz Aguirre-López, Leonardo Peraza-Reyes

{"title":"Organelle activity organized by the endoplasmic reticulum-mitochondria encounter structure -ERMES- is essential for Podospora anserina development.","authors":"Melisa Álvarez-Sánchez, Matías Ramírez-Noguez, Beatriz Aguirre-López, Leonardo Peraza-Reyes","doi":"10.15698/mic2025.09.860","DOIUrl":"10.15698/mic2025.09.860","url":null,"abstract":"Eucaryotic cell functioning and development depend on the concerted activity of its organelles. In the model fungus Podospora anserina, sexual development involves a dynamic regulation of mitochondria, peroxisomes and the endoplasmic reticulum (ER), suggesting that their activity during this process is coordinated. The ER-Mitochondria Encounter Structure (ERMES) is a tether complex composed of the ER protein Mmm1 and the mitochondrial proteins Mdm10, Mdm12 and Mdm34, which mediates membrane contact-site formation between these organelles. This complex also mediates interactions between mitochondria and peroxisomes. Here we analyzed the role of the ERMES complex during P. anserina development. By studying a thermosensitive MDM10 mutant, we show that MDM10 is required for mitochondrial morphology and distribution, as well as for peroxisome membrane-remodeling and motility. We discovered that lipid droplets exhibit a subapical hyphal localization, which depends on MDM10. MDM10 is also required for ER shaping and dynamics, notably of the apical ER domains of the polarized-growing hyphal region, in a process that involves the activity of the protein YOP1. We also show that apical ER shaping involves a Spitzenkörper-associated membrane traffic, which implicates MDM10, and that the mycelial growth defect of mdm10 mutants is exacerbated when the ER-shaping proteins YOP1 or RTN1 are loss. Finaly, we show that MMM1 is strictly required for mycelial growth and sexual development, suggesting that its activity is essential. Our results show that the activity of distinct organelles depends on the ERMES complex, and that the function of this complex is critical for P. anserina growth and development.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"255-273"},"PeriodicalIF":3.9,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The molecular mechanisms and physiological roles of mitochondria dynamics in Saccharomyces cerevisiae. 酿酒酵母线粒体动力学的分子机制及其生理作用。

IF 3.9 3区生物学

Microbial Cell Pub Date : 2025-08-27 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.08.859

Chang-Lin Chen, Wei-Ling Huang, Alexander Rapoport, Rimantas Daugelavičius, Chuang-Rung Chang

{"title":"The molecular mechanisms and physiological roles of mitochondria dynamics in Saccharomyces cerevisiae.","authors":"Chang-Lin Chen, Wei-Ling Huang, Alexander Rapoport, Rimantas Daugelavičius, Chuang-Rung Chang","doi":"10.15698/mic2025.08.859","DOIUrl":"10.15698/mic2025.08.859","url":null,"abstract":"Mitochondria are essential organelles that form a dynamic network within cells. The fusion, fission, and transport processes among mitochondria must reach a balance, which is achieved through complex regulatory mechanisms. These dynamic processes and regulatory pathways are highly conserved across species and are coordinated to help cells respond to environmental stress. The budding yeast Saccharomyces cerevisiae has become an important model organism for studying mitochondria dynamics due to its genetic tractability and the conservation of key mitochondrial regulators. Previous research on mitochondria dynamics in yeast has provided valuable insights into the regulatory pathways in eukaryotic cells. It has helped to elucidate the mechanisms related to diseases associated with disrupted mitochondria dynamics. This review explores the molecular mechanisms underlying mitochondria dynamics and their physiological roles in Saccharomyces cerevisiae. The knowledge we learned from the primary eukaryotic yeast cell will aid us in advancing future research on the regulatory mechanisms of mitochondria in both health and disease.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"242-254"},"PeriodicalIF":3.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alternative splicing drives a dynamic transcriptomic response during Acanthamoeba castellanii programmed cell death. 在棘阿米巴castellanii程序性细胞死亡期间，选择性剪接驱动动态转录组反应。

IF 3.9 3区生物学

Microbial Cell Pub Date : 2025-08-26 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.08.858

Jesús Gómez-Montalvo, Zisis Koutsogiannis, Sutherland K Maciver, Alvaro de Obeso Fernández Del Valle

{"title":"Alternative splicing drives a dynamic transcriptomic response during Acanthamoeba castellanii programmed cell death.","authors":"Jesús Gómez-Montalvo, Zisis Koutsogiannis, Sutherland K Maciver, Alvaro de Obeso Fernández Del Valle","doi":"10.15698/mic2025.08.858","DOIUrl":"10.15698/mic2025.08.858","url":null,"abstract":"Programmed cell death (PCD) in unicellular organisms is not well characterized. This study investigated the transcriptomic response of Acanthamoeba castellanii to G418-induced PCD, focusing on the role of alternative splicing (AS). RNA sequencing revealed extensive transcriptional changes, affecting approximately 70% of annotated genes over six hours of treatment. This analysis also highlighted significant alterations in pathways related to cell cycle, proteolysis, and RNA splicing. Analysis of AS events identified 18,748 differentially spliced events, predominantly intron retention (IR). Interestingly, retained introns displayed a 3' bias in untreated cells, a pattern that shifted towards uniform distribution throughout the gene body during PCD. Additionally, we characterized retained introns during trophozoite stage and during PCD of the amoeba. Correlational analysis revealed a significant negative correlation between IR and transcript levels, suggesting a complex interplay between transcriptional and post-transcriptional regulation. The predominance of IR, coupled with its dynamic positional shift during PCD, points to a novel regulatory mechanism in A. castellanii PCD. These findings provide insights into the molecular mechanisms underlying PCD in this organism, potentially identifying new therapeutic targets and allowing us a better understanding of such process in A. castellanii, a facultative human pathogen.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"231-241"},"PeriodicalIF":3.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut microbiota and ankylosing spondylitis: current insights and future challenges. 肠道微生物群与强直性脊柱炎：当前的见解和未来的挑战。

IF 3.9 3区生物学

Microbial Cell Pub Date : 2025-08-25 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.08.857

Andrei Lobiuc, Liliana Groppa, Lia Chislari, Eugeniu Russu, Marinela Homitchi, Camelia Ciorescu, Sevag Hamamah, I Codruta Bran, Mihai Covasa

{"title":"Gut microbiota and ankylosing spondylitis: current insights and future challenges.","authors":"Andrei Lobiuc, Liliana Groppa, Lia Chislari, Eugeniu Russu, Marinela Homitchi, Camelia Ciorescu, Sevag Hamamah, I Codruta Bran, Mihai Covasa","doi":"10.15698/mic2025.08.857","DOIUrl":"10.15698/mic2025.08.857","url":null,"abstract":"Ankylosing spondylitis (AS) is a chronic inflammatory disease with complex pathogenesis influenced by genetic, immunological and environmental factors. Recent evidence suggests that gut microbiota significantly contributes to AS etiopathogenesis. Dysbiosis and altered immune responses in the gut potentially trigger or exacerbate the disease through intestinal barrier disruption, alteration of the IL-23/17 axis and metabolite production. This review explores the growing role of gut microbiota in AS and its potential to reshape targeted treatment strategies and facilitate development of adjunct therapies to address disease onset and progression. AS is a multifactorial disease in which gut dysbiosis plays a significant role influencing immune regulation notably through the IL-23/17 pathway. Alterations in gut microbiota composition and its metabolites contribute to systemic inflammation, reinforcing a self-perpetuating feedback loop between gut and spinal inflammation that drives disease progression. Emerging evidence has linked microbial mechanisms to HLA-B27 misfolding promoting endoplasmic reticulum stress and triggering molecular mimicry through gut microbial-associated molecular patterns further contributing to AS pathogenesis. Given the crucial role of gut microbiota in AS, targeting microbiota imbalances presents a promising avenue for novel therapeutic strategies. Although it remains unclear whether gut inflammation and microbial changes precedes AS onset, current evidence suggests an ongoing cycle of autoimmune inflammation involving both the gut and joints. Further research, particularly longitudinal studies, are needed to better understand the gut-joint axis and its potential therapeutic implications in AS management.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"210-230"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of the putative sit1 gene in normal germination of spores and virulence of the Mucor lusitanicus. 假定的sit1基因在lusitanicus毛霉孢子正常萌发和毒力中的作用。

IF 3.9 3区生物学

Microbial Cell Pub Date : 2025-08-12 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.08.856

Bernadett Vágó, Kitti Bauer, Naomi Varghese, Sándor Kiss-Vetráb, Sándor Kocsubé, Mónika Varga, András Szekeres, Csaba Vágvölgyi, Tamás Papp, Gábor Nagy

{"title":"Role of the putative sit1 gene in normal germination of spores and virulence of the Mucor lusitanicus.","authors":"Bernadett Vágó, Kitti Bauer, Naomi Varghese, Sándor Kiss-Vetráb, Sándor Kocsubé, Mónika Varga, András Szekeres, Csaba Vágvölgyi, Tamás Papp, Gábor Nagy","doi":"10.15698/mic2025.08.856","DOIUrl":"10.15698/mic2025.08.856","url":null,"abstract":"Mucormycosis is a life-threatening infection caused by certain members of the fungal order Mucorales, with increased incidence in recent years. Individuals with untreated diabetes mellitus, and patients treated with deferoxamine are particularly susceptible to this infection. Elevated free iron concentrations in serum contribute to the development of mucormycosis. Pathogenic fungi have evolved multiple mechanisms to acquire and utilize free iron or extract it from the various iron-binding molecules within the host. The utilization of hydroxamate siderophores as xenosiderophores may contribute to the development of mucormycosis. The genome of Mucor lusitanicus encodes one Sit1 siderophore transporter. In this study, the role of the sit1 gene was characterized by generating knockout mutants using CRISPR-Cas9. Relative transcript level of the sit1 gene significantly increased in the presence of deferoxamine- and deferasirox-iron complexes. Lack of sit1 resulted in altered germination of spores and growth ability, and decreased virulence. Furthermore, absence of the gene caused elevated transcript levels of a ferric reductase (FRE), a low-affinity iron permease (FET4) and a copper dependent iron oxidase (FET3). Our result suggests that expressions of the genes involved in iron uptake affect each other. The lack of Sit1 resulted in an increased transcript level of the FRE3 gene, which may be able to reduce iron from the siderophore-iron complex. The reduced and liberated iron may be then taken up by activated FET4a. This study highlights the significance of understanding the iron acquisition mechanisms of pathogenic fungi to develop effective treatments for fungal infections.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"195-209"},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor microenvironment signatures enhances lung adenocarcinoma prognosis prediction: Implication of intratumoral microbiota. 肿瘤微环境特征增强肺腺癌预后预测：肿瘤内微生物群的意义。

IF 3.9 3区生物学

Microbial Cell Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.08.855

Fei Zhao, Lei Wang, Dongjie Du, Heaven Zhao, Geng Tian, Yufeng Li, Yankun Liu, Zhiwu Wang, Dasheng Liu, Jingwu Li, Lei Ji, Hong Zhao

{"title":"Tumor microenvironment signatures enhances lung adenocarcinoma prognosis prediction: Implication of intratumoral microbiota.","authors":"Fei Zhao, Lei Wang, Dongjie Du, Heaven Zhao, Geng Tian, Yufeng Li, Yankun Liu, Zhiwu Wang, Dasheng Liu, Jingwu Li, Lei Ji, Hong Zhao","doi":"10.15698/mic2025.08.855","DOIUrl":"10.15698/mic2025.08.855","url":null,"abstract":"The interaction between intratumoral microbiome and the tumor microenvironment (TME) has furthered our understanding of tumor ecology. Yet, the implications of their interaction for lung cancer management remain unclear. In the current work, we collected host transcriptome samples and matched intratumoral microbiome samples, as well as detailed clinical metadata from The Cancer Genome Atlas (TCGA) of 478 patients with lung adenocarcinoma (LUAD). Utilizing the multiomics integration approach, we comprehensively investigated the crosstalk between the TME and intratumoral microbiome in patients with LUAD. First, we developed a prognostic model based on the TME signatures (TMEindex) that clearly distinguished clinical, survival, and response to immunotherapy of patients with LUAD. Additionally, we found profound differences in intratumoral microbiota signatures, including alpha- and beta-diversity, among patients with different survival risks based on the TME signatures. In depth, we detected that genera Luteibacter and Chryseobacterium were strongly negatively and positively associated with patients' survival risk, respectively, suggesting their opposing roles in cancer progression. Moreover, we developed a model that fused intratumoral microbial abundance information with TME signatures, called intratumoral microbiome-modified TMEindex (IMTMEindex), leading in predicting patient overall survival at 1-, 3-, and 5-years. Future clinical profiling of the specific intratumoral microbes in the TME could improve prognosis, inform immunotherapy, and facilitate the development of novel therapeutics for LUAD.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"182-194"},"PeriodicalIF":3.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Persistence phenotype of adherent-invasive Escherichia coli in response to ciprofloxacin, revealing high-persistence strains. 黏附-侵袭性大肠杆菌对环丙沙星反应的持久性表型，揭示高持久性菌株。

IF 3.9 3区生物学

Microbial Cell Pub Date : 2025-07-11 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.07.854

Valeria Pérez-Villalobos, Roberto Vidal, Marcela A Hermoso, Paula Bustamante

{"title":"Persistence phenotype of adherent-invasive Escherichia coli in response to ciprofloxacin, revealing high-persistence strains.","authors":"Valeria Pérez-Villalobos, Roberto Vidal, Marcela A Hermoso, Paula Bustamante","doi":"10.15698/mic2025.07.854","DOIUrl":"10.15698/mic2025.07.854","url":null,"abstract":"Persister cells are a subpopulation of bacteria capable of surviving antibiotic treatments and are thought to contribute to disease chronicity and symptom relapse of chronic conditions. Crohn's disease (CD) is a multifactorial chronic inflammatory condition of the gastrointestinal tract, and adherent-invasive Escherichia coli (AIEC) have emerged as a key contributor to its pathogenesis. AIEC can survive, replicate, and produce persister cells within macrophages; however, beyond the LF82 reference strain, little is known about the persistence phenotype and its variability among AIEC strains. In this study, the survival of two AIEC reference strains was analyzed following ciprofloxacin treatment, a fluoroquinolone antibiotic commonly used in CD therapy. In addition, four AIEC clinical isolates and two non-AIEC E. coli pathotypes were included for comparison. We investigated the roles of the resident antibiotic resistance plasmid, the stress response protein HtrA, and macrophage-induced persister formation. Our results revealed broad variability in persister cell formation among AIEC strains. Remarkably, the reference NRG857c strain exhibits a threateningly high-persistence phenotype, with persistence levels 200-fold higher than LF82 and certain clinical isolates. Neither the antibiotic resistance plasmid nor HtrA were required for this phenotype. Moreover, unlike LF82, NRG857c did not exhibit increased persistence following macrophage internalization. Overall, our findings demonstrate the presence of distinct persistence phenotypes among AIEC strains and identify NRG857c as a high-persistence variant. These observations underscore the need to consider bacterial persistence in the management of CD, particularly given the potential presence of AIEC strains with elevated persistence capabilities.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"173-181"},"PeriodicalIF":3.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knocking out histidine ammonia-lyase by using CRISPR-Cas9 abolishes histidine role in the bioenergetics and the life cycle of Trypanosoma cruzi. 利用CRISPR-Cas9敲除组氨酸解氨酶可消除组氨酸在克氏锥虫生物能学和生命周期中的作用。

IF 4.1 3区生物学

Microbial Cell Pub Date : 2025-06-25 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.06.853

Janaína de Freitas Nascimento, María Julia Barisón, Gabriela Torres Montanaro, Letícia Marchese, Rodolpho Ornitz Oliveira Souza, Letícia Sophia Silva, Alessandra Aparecida Guarnieri, Ariel Mariano Silber

{"title":"Knocking out histidine ammonia-lyase by using CRISPR-Cas9 abolishes histidine role in the bioenergetics and the life cycle of Trypanosoma cruzi.","authors":"Janaína de Freitas Nascimento, María Julia Barisón, Gabriela Torres Montanaro, Letícia Marchese, Rodolpho Ornitz Oliveira Souza, Letícia Sophia Silva, Alessandra Aparecida Guarnieri, Ariel Mariano Silber","doi":"10.15698/mic2025.06.853","DOIUrl":"10.15698/mic2025.06.853","url":null,"abstract":"Trypanosoma cruzi, the causing agent of Chagas disease, is the only known trypanosomatid pathogenic to humans having a complete histidine to glutamate pathway, which involves a series of four enzymatic reactions that convert histidine into downstream metabolites, including urocanate, 4-imidazolone-5-propionate, N-formimino-L-glutamate and L-glutamate. Recent studies have highlighted the importance of this pathway in ATP production, redox balance, and the maintenance of cellular homeostasis in T. cruzi. In this work, we focus on the first step of the histidine degradation pathway, which is performed by the enzyme histidine ammonia lyase. Here we determined the kinetic and biochemical parameters of the T. cruzi histidine ammonia-lyase. By generating null mutants of this enzyme using CRISPR-Cas9 we observed that disruption of the first step of the histidine degradation pathway completely abolishes the capability of this parasite to metabolise histidine, compromising the use of this amino acid as an energy and carbon source. Additionally, we showed that the knockout of the histidine ammonia lyase affects metacyclogenesis when histidine is the only metabolizable source and diminishes trypomastigote infection in vitro.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"157-172"},"PeriodicalIF":4.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dissecting the cell cycle regulation, DNA damage sensitivity and lifespan effects of caffeine in fission yeast. 剖析分裂酵母中咖啡因的细胞周期调控、DNA损伤敏感性和寿命效应。

IF 4.1 3区生物学

Microbial Cell Pub Date : 2025-06-24 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.06.852

John-Patrick Alao, Juhi Kumar, Despina Stamataki, Charalampos Rallis

{"title":"Dissecting the cell cycle regulation, DNA damage sensitivity and lifespan effects of caffeine in fission yeast.","authors":"John-Patrick Alao, Juhi Kumar, Despina Stamataki, Charalampos Rallis","doi":"10.15698/mic2025.06.852","DOIUrl":"10.15698/mic2025.06.852","url":null,"abstract":"Caffeine can modulate cell cycle progression, override DNA damage checkpoint signalling and increase chronological lifespan (CLS) in various model systems. Early studies suggested that caffeine inhibits the phosphatidylinositol 3-kinase-related kinase (PIKK) Rad3 to override DNA damage-induced cell cycle arrest in fission yeast. We have previously suggested that caffeine modulates cell cycle progression and lifespan by inhibiting the Target of Rapamycin Complex 1 (TORC1). Nevertheless, whether this inhibition is direct or not, has remained elusive. TORC1 controls metabolism and mitosis timing by integrating nutrients and environmental stress response (ESR) signalling. Nutritional or other stresses activate the Sty1-Ssp1-Ssp2 (AMP-activated protein kinase complex, AMPK) pathway, which inhibits TORC1 and accelerates mitosis through Sck2 inhibition. Additionally, activation of the ESR pathway can extend lifespan in fission yeast. Here, we demonstrate that caffeine indirectly activates Ssp1, Ssp2 and the AMPKβ regulatory subunit Amk2 to advance mitosis. Ssp2 is phosphorylated in an Ssp1-dependent manner following exposure to caffeine. Furthermore, Ssp1 and Amk2, are required for resistance to caffeine under conditions of prolonged genotoxic stress. The effects of caffeine on DNA damage sensitivity are uncoupled from mitosis in AMPK pathway mutants. We propose that caffeine interacts synergistically with other genotoxic agents to increase DNA damage sensitivity. Our findings show that caffeine accelerates mitotic division and is beneficial for CLS through AMPK. Direct pharmacological targeting of AMPK may serve towards healthspan and lifespan benefits beyond yeasts, given the highly conserved nature of this key regulatory cellular energy sensor.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"141-156"},"PeriodicalIF":4.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis. Uga3通过调节精氨酸生物合成影响酿酒酵母的氮代谢。

IF 4.1 3区生物学

Microbial Cell Pub Date : 2025-06-12 eCollection Date: 2025-01-01 DOI: 10.15698/mic2025.06.851

Nicolás Urtasun, Sebastián Aníbal Muñoz, Martín Arán, Mariana Bermúdez-Moretti

{"title":"Uga3 influences nitrogen metabolism in Saccharomyces cerevisiae by modulating arginine biosynthesis.","authors":"Nicolás Urtasun, Sebastián Aníbal Muñoz, Martín Arán, Mariana Bermúdez-Moretti","doi":"10.15698/mic2025.06.851","DOIUrl":"10.15698/mic2025.06.851","url":null,"abstract":"Nitrogen metabolism in Saccharomyces cerevisiae is tightly regulated to optimize the utilization of available nitrogen sources. Uga3 is a known transcription factor involved in the gamma-aminobutyric acid (GABA) pathway; however, its broader role in nitrogen metabolism remains unclear. Here, we demonstrate that Uga3 influences arginine biosynthesis, linking its function beyond GABA utilization when cells grow with proline as the sole and poor nitrogen source. Using a combination of intracellular amino acid quantification, proteomics, and gene expression analysis, we show that the absence of Uga3 leads to a significant increase in intracellular arginine levels and the up-regulation of ARG5,6, a key gene in the arginine biosynthesis pathway. Proteomic analysis of uga3∆ cells reveals differential expression of multiple nitrogen metabolism-related proteins, suggesting a broader regulatory role for Uga3. Surprisingly, chromatin immunoprecipitation (ChIP) assays indicate that Uga3 does not directly bind the ARG5,6 promoter, implying an indirect regulatory mechanism. These findings expand the known functions of Uga3, positioning it as a key player in the coordinated regulation of nitrogen metabolism. Given the impact of nitrogen availability on industrial fermentation processes, our results provide new insights into optimizing yeast performance under nitrogen-limited conditions.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"12 ","pages":"132-140"},"PeriodicalIF":4.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0