Molecular and Cellular Biology最新文献_第2页

Causes, Consequences and Challenges of Intron Retention in lncRNAs. lncrna中内含子保留的原因、后果和挑战。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-08-08 DOI: 10.1080/10985549.2025.2539755

Manish Kumar, Ioannis Grammatikakis

引用次数: 0

A Mutation in the RNA-Binding Protein Cth2 Limits the Adaptation of a Subset of Wild Saccharomyces cerevisiae Yeast Strains to Iron Deficiency. rna结合蛋白Cth2的突变限制了野生酿酒酵母菌株对铁缺乏的适应。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-08-04 DOI: 10.1080/10985549.2025.2539754

Elena Valera-García, Raquel Sorribes-Dauden, Sergi Puig

{"title":"A Mutation in the RNA-Binding Protein Cth2 Limits the Adaptation of a Subset of Wild Saccharomyces cerevisiae Yeast Strains to Iron Deficiency.","authors":"Elena Valera-García, Raquel Sorribes-Dauden, Sergi Puig","doi":"10.1080/10985549.2025.2539754","DOIUrl":"https://doi.org/10.1080/10985549.2025.2539754","url":null,"abstract":"Iron is an essential micronutrient for eukaryotic organisms. In response to iron deficiency, the yeast Saccharomyces cerevisiae optimizes iron utilization by downregulating nonessential iron-dependent processes, such as mitochondrial respiration. This regulatory mechanism is mediated by a mRNA-binding protein designated Cth2. In response to iron scarcity, Cth2 binds through its tandem zinc-finger (TFZ) domain to multiple mRNAs encoding proteins that are necessary for iron-dependent pathways. This binding limits the expression of these mRNAs by promoting their degradation and inhibiting their translation. In this study, we have examined a set of wild yeast strains that share a G195R mutation within the Cth2 TZF domain. By genetically editing both laboratory and wild yeast strains, we demonstrate that the Cth2-G195R protein is defective in binding and degradation of its target transcripts, and it accumulates in the nucleus of the cell, leading to a significant growth defect in iron-deficient conditions. Some of these wild yeast strains also display enhanced tolerance to high iron conditions, indicating that they have adapted to environments with elevated iron levels and have consequently diminished their capacity to grow in iron-limiting conditions. These findings highlight the crucial function of Cth2 in enabling yeast cells to adapt to iron-deficient environments.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775802","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

Expression of Concern: Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling. 关注表达：丝裂原刺激与端粒缩短共同激活DNA损伤反应和衰老信号。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-02-24 DOI: 10.1080/10985549.2025.2462481

引用次数: 0

Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway. 在缺乏典型atg5依赖性自噬起始途径的情况下，激酶抑制剂诱导细胞型特异性液泡形成。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-02-02 DOI: 10.1080/10985549.2025.2454421

Susan Jose, Himanshi Sharma, Janki Insan, Khushboo Sharma, Varun Arora, Sameera Puranapanda, Sonam Dhamija, Nabil Eid, Manoj B Menon

{"title":"Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway.","authors":"Susan Jose, Himanshi Sharma, Janki Insan, Khushboo Sharma, Varun Arora, Sameera Puranapanda, Sonam Dhamija, Nabil Eid, Manoj B Menon","doi":"10.1080/10985549.2025.2454421","DOIUrl":"10.1080/10985549.2025.2454421","url":null,"abstract":"Pyridinyl-imidazole class p38 MAPKα/β (MAPK14/MAPK11) inhibitors including SB202190 have been shown to induce cell-type specific defective autophagy resulting in micron-scale vacuole formation, cell death, and tumor suppression. We had earlier shown that this is an off-target effect of SB202190. Here we provide evidence that this vacuole formation is independent of ATG5-mediated canonical autophagosome initiation. While SB202190 interferes with autophagic flux in many cell lines parallel to vacuolation, autophagy-deficient DU-145 cells and CRISPR/Cas9 gene-edited ATG5-knockout A549 cells also undergo vacuolation upon SB202190 treatment. Late-endosomal GTPase RAB7 colocalizes with these compartments and RAB7 GTP-binding is essential for SB202190-induced vacuolation. A screen for modulators of SB202190-induced vacuolation revealed molecules including multi-kinase inhibitor sorafenib as inhibitors of vacuolation and sorafenib co-treatment enhanced cytotoxicity of SB202190. Moreover, VE-821, an ATR inhibitor was found to phenocopy the cell-type specific vacuolation response of SB202190. To identify the factors determining the cell-type specificity of vacuolation induced by SB-compounds and VE-821, we compared the transcriptomics data from vacuole-forming and non-vacuole-forming cancer cell lines and identified a gene expression signature that may define sensitivity of cells to these small-molecules. Further analyses using small molecule tools and the gene signature discovered here, could reveal novel mechanisms regulating this interesting anti-cancer phenotype.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"99-115"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080547","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

SIRT3 Deficiency Promotes Lung Endothelial Pyroptosis Through Impairing Mitophagy to Activate NLRP3 Inflammasome During Sepsis-Induced Acute Lung Injury. 在脓毒症诱导的急性肺损伤过程中，SIRT3缺陷通过损害有丝分裂来激活NLRP3炎症体，从而促进肺内皮细胞脓毒症。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1080/10985549.2024.2426282

Congmin Yan, Xin Lin, Jingting Guan, Wengang Ding, Ziyong Yue, Zhiqiang Tang, Xiangqi Meng, Bo Zhao, Zhiqiang Song, Dongmei Li, Tao Jiang

{"title":"SIRT3 Deficiency Promotes Lung Endothelial Pyroptosis Through Impairing Mitophagy to Activate NLRP3 Inflammasome During Sepsis-Induced Acute Lung Injury.","authors":"Congmin Yan, Xin Lin, Jingting Guan, Wengang Ding, Ziyong Yue, Zhiqiang Tang, Xiangqi Meng, Bo Zhao, Zhiqiang Song, Dongmei Li, Tao Jiang","doi":"10.1080/10985549.2024.2426282","DOIUrl":"10.1080/10985549.2024.2426282","url":null,"abstract":"Acute lung injury (ALI) is a major cause of death in bacterial sepsis due to endothelial inflammation and endothelial permeability defects. Mitochondrial dysfunction is recognized as a key mediator in the pathogenesis of sepsis-induced ALI. Sirtuin 3 (SIRT3) is a histone protein deacetylase involved in preservation of mitochondrial function, which has been demonstrated in our previous study. Here, we investigated the effects of SIRT3 deficiency on impaired mitophagy to promote lung endothelial cells (ECs) pyroptosis during sepsis-induced ALI. We found that 3-TYP aggravated sepsis-induced ALI with increased lung ECs pyroptosis and enhanced NLRP3 activation. Mitochondrial reactive oxygen species (mtROS) and extracellular mitochondrial DNA (mtDNA) released from damaged mitochondria could be exacerbated in SIRT3 deficiency, which further elicit NLRP3 inflammasome activation in lung ECs during sepsis-induced ALI. Furthermore, Knockdown of SIRT3 contributed to impaired mitophagy via downregulating Parkin, which resulted in mitochondrial dysfunction. Moreover, pharmacological inhibition NLRP3 or restoration of SIRT3 attenuates sepsis-induced ALI and sepsis severity in vivo. Taken together, our results demonstrated SIRT3 deficiency facilitated mtROS production and cytosolic release of mtDNA by impaired Parkin-dependent mitophagy, promoting to lung ECs pyroptosis through the NLRP3 inflammasome activation, which providing potential therapeutic targets for sepsis-induced ALI.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647859","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

Key Mechanisms in Lysosome Stability, Degradation and Repair. 溶酶体稳定性、降解和修复的关键机制。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-05-09 DOI: 10.1080/10985549.2025.2494762

Rui Zhang, Marc A Vooijs, Tom Gh Keulers

{"title":"Key Mechanisms in Lysosome Stability, Degradation and Repair.","authors":"Rui Zhang, Marc A Vooijs, Tom Gh Keulers","doi":"10.1080/10985549.2025.2494762","DOIUrl":"10.1080/10985549.2025.2494762","url":null,"abstract":"Lysosomes are organelles that play pivotal roles in macromolecule digestion, signal transduction, autophagy, and cellular homeostasis. Lysosome instability, including the inhibition of lysosomal intracellular activity and the leakage of their contents, is associated with various pathologies, including cancer, neurodegenerative diseases, inflammatory diseases and infections. These lysosomal-related pathologies highlight the significance of factors contributing to lysosomal dysfunction. The vulnerability of the lysosomal membrane and its components to internal and external stimuli make lysosomes particularly susceptible to damage. Cells are equipped with mechanisms to repair or degrade damaged lysosomes to prevent cell death. Understanding the factors influencing lysosome stabilization and damage repair is essential for developing effective therapeutic interventions for diseases. This review explores the factors affecting lysosome acidification, membrane integrity, and functional homeostasis and examines the underlying mechanisms of lysosomal damage repair. In addition, we summarize how various risk factors impact lysosomal activity and cell fate.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"212-224"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018298","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}

引用次数: 0

Hypoxia Signaling in the Cell Type-Specific Regulation of Erythropoietin Production Throughout Mammalian Development. 缺氧信号在哺乳动物发育过程中对促红细胞生成素产生的细胞类型特异性调节。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-06-27 DOI: 10.1080/10985549.2025.2522720

Norio Suzuki, Taku Nakai, Yuma Iwamura, Koichiro Kato

{"title":"Hypoxia Signaling in the Cell Type-Specific Regulation of Erythropoietin Production Throughout Mammalian Development.","authors":"Norio Suzuki, Taku Nakai, Yuma Iwamura, Koichiro Kato","doi":"10.1080/10985549.2025.2522720","DOIUrl":"10.1080/10985549.2025.2522720","url":null,"abstract":"To maintain the oxygen supply to peripheral organs, the production of erythropoietin (EPO), an essential growth factor for red blood cells, is controlled in a hypoxia-inducible manner in mammals. The developmentally earliest site of EPO production, which is necessary for primitive erythropoiesis in the yolk sac and bloodstream, is found in a subset of neural crest and neuroepithelial cells during mid-stage embryonic development. These neural EPO-producing (NEP) cells maintain their immaturity and EPO-producing ability in their hypoxic microenvironment, which is inherent in developing embryos. After oxygenation of the fetus by the establishment of the circulatory system and EPO-driven erythropoiesis, the site of EPO production shifts to hepatocytes of the fetal liver, where erythropoiesis also occurs. In adult mammals, a specific fibroblastic cell fraction in the renal interstitium, known as renal EPO-producing (REP) cells, secretes the majority of EPO to support bone marrow erythropoiesis. Hypoxia-inducible transcription factors (HIFs) are involved in EPO production across NEP cells, hepatocytes, and REP cells, whereas the regulatory mechanisms are distinct for each cell type. This review summarizes the molecular mechanisms of EPO gene regulation throughout all life stages and discusses the associations of HIF signaling in EPO production with other stimuli, including inflammation and metabolism.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"386-394"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506558","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

Erythropoietin Production in Embryonic Neural Cells is Controlled by Hypoxia Signaling and Histone Deacetylases with an Undifferentiated Cellular State. 胚胎神经细胞中促红细胞生成素的产生受缺氧信号和未分化细胞状态组蛋白去乙酰化酶的控制。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1080/10985549.2024.2428717

Yuma Iwamura, Taku Nakai, Koichiro Kato, Hirotaka Ishioka, Masayuki Yamamoto, Ikuo Hirano, Norio Suzuki

{"title":"Erythropoietin Production in Embryonic Neural Cells is Controlled by Hypoxia Signaling and Histone Deacetylases with an Undifferentiated Cellular State.","authors":"Yuma Iwamura, Taku Nakai, Koichiro Kato, Hirotaka Ishioka, Masayuki Yamamoto, Ikuo Hirano, Norio Suzuki","doi":"10.1080/10985549.2024.2428717","DOIUrl":"10.1080/10985549.2024.2428717","url":null,"abstract":"During mammalian development, production sites of the erythroid growth factor erythropoietin (EPO) shift from the neural tissues to the liver in embryos and to the kidneys in adults. Embryonic neural EPO-producing (NEP) cells, a subpopulation of neuroepithelial and neural crest cells, express the Epo gene between embryonic day (E) 8.5 and E11.5 to promote primitive erythropoiesis in mice. While Epo gene expression in the liver and kidneys is induced under hypoxic conditions through hypoxia-inducible transcription factors (HIFs), the Epo gene regulatory mechanisms in NEP cells remain to be elucidated. Here, we confirmed the presence of cells co-expressing EPO and HIFs in mouse neural tubes, where the hypoxic microenvironment activates HIFs. Chemical activation and inhibition of HIFs demonstrated the hypoxic regulation of EPO expression in human fetal neural progenitors and mouse embryonic neural tissues. In addition, we found that histone deacetylase inhibitors can reactivate EPO production in cell lines derived from NEP cells and human neuroblastoma, as well as in mouse primary neural crest cells, while rejuvenating these cells. Furthermore, the ability of the rejuvenated cells to produce EPO was maintained in hypoxia. Thus, EPO production is controlled by epigenetic mechanisms and hypoxia signaling in the immature state of hypoxic NEP cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"32-45"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770614","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

ALYREF Promotes Progression of Intrahepatic Cholangiocarcinoma through Increasing the Level of Isocitrate Dehydrogenase 1 in an m5C-Dependent Manner. ALYREF通过以m5c依赖的方式增加异柠檬酸脱氢酶1的水平，促进肝内胆管癌的进展。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-05-14 DOI: 10.1080/10985549.2025.2490031

Zhiqiang Hao, Haixiang Yang, Wei Zhu, Dedong Yu, Yanjie Cao, Yun Wu

{"title":"ALYREF Promotes Progression of Intrahepatic Cholangiocarcinoma through Increasing the Level of Isocitrate Dehydrogenase 1 in an m5C-Dependent Manner.","authors":"Zhiqiang Hao, Haixiang Yang, Wei Zhu, Dedong Yu, Yanjie Cao, Yun Wu","doi":"10.1080/10985549.2025.2490031","DOIUrl":"https://doi.org/10.1080/10985549.2025.2490031","url":null,"abstract":"RNA 5-methylcytosine (m5C) modification has emerged as an important regulatory mechanism in the progression of human cancers, including hepatobiliary tumors. The m5C \"reader\" Aly/REF export factor (ALYREF) was recently found to be identified as a prognostic biomarker in liver cancer. However, its exact role in intrahepatic cholangiocarcinoma (ICC) progression is unclear. In this study, ALYREF was found to be upregulated in ICC tissues and cells. The gain- and loss-of-function experiments indicated that ALYREF promoted cell proliferation and invasion and suppressed cell apoptosis. Moreover, we found that isocitrate dehydrogenase 1 (IDH1), a metastatic marker of liver cancer, was also upregulated in ICC tissues, displayed a relatively strong positive correlation with the level of ALYREF, and was positively regulated by ALYREF. As an m5C \"reader\", ALYREF interacted with m5C-IDH1 mRNA and increased its stability. ALYREF knockdown partially eliminated the promotion of IDH1 on ICC cell proliferation and invasion. ALYREF positively regulated NRF2-driven glutathione synthesis in ICC cells, which was reversed by IDH1 silencing. Finally, in a xenograft tumor mouse model, knockdown of ALYREF or treatment with ivosidenib (an IDH1 inhibitor) significantly suppressed tumor growth in vivo. In conclusion, ALYREF promotes ICC progression by increasing IDH1 levels in an m5C-dependent manner.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"45 5","pages":"198-211"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079054","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

Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria. 了解胱氨酸-合成酶基因突变的影响：探索同型半胱氨酸尿的新疗法。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-06-10 DOI: 10.1080/10985549.2025.2511338

Tomas Majtan, Ela Mijatovic, Maria Petrosino

{"title":"Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria.","authors":"Tomas Majtan, Ela Mijatovic, Maria Petrosino","doi":"10.1080/10985549.2025.2511338","DOIUrl":"10.1080/10985549.2025.2511338","url":null,"abstract":"Protein misfolding and conformational instability drive protein conformational disorders, causing either accelerated degradation and loss-of-function, as in inherited metabolic disorders like lysosomal storage disorders, or toxic aggregation and gain-of-function, as in neurodegenerative diseases like Alzheimer's disease or amyotrophic lateral sclerosis. Classical homocystinuria (HCU), an inborn error of sulfur amino acid metabolism, results from cystathionine beta-synthase (CBS) deficiency. CBS regulates methionine conversion into metabolites critical for redox balance (cysteine, glutathione) and signaling (H2S). Pathogenic missense mutations in the CBS gene often impair folding, cofactor binding, stability or oligomerization rather than targeting the key catalytic residues of the CBS enzyme. Advances in understanding of CBS folding and assembly as well as CBS interactions with cellular proteostasis network offer potential for therapies using pharmacological chaperones (PCs), i.e., compounds facilitating proper folding, assembly or cellular trafficking. This review discusses progress in identifying PCs for HCU, including chemical chaperones, cofactors, and proteasome inhibitors. We outline future directions, focusing on high-throughput screening and structure-based drug design to develop CBS-specific PCs. These could stabilize mutant CBS, enhance its stability and restore activity, providing new treatments for HCU and possibly other conditions related to dysregulated CBS, such as cancer or Down's syndrome.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"327-342"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266709","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