Journal of cell science最新文献_第4页

MitoRUSH as a tool to study the efficiency of mitochondrial import in complex I-deficient cells. MitoRUSH作为研究线粒体输入效率的工具在复杂i缺乏细胞。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-09 DOI: 10.1242/jcs.263701

Michal Wasilewski, Karthik Mohanraj, Maciej Zakrzewski, Remigiusz A Serwa, Agnieszka Chacinska

{"title":"MitoRUSH as a tool to study the efficiency of mitochondrial import in complex I-deficient cells.","authors":"Michal Wasilewski, Karthik Mohanraj, Maciej Zakrzewski, Remigiusz A Serwa, Agnieszka Chacinska","doi":"10.1242/jcs.263701","DOIUrl":"https://doi.org/10.1242/jcs.263701","url":null,"abstract":"Most mitochondrial proteins are imported through the actions of the presequence translocase of the inner membrane, the TIM23 complex, which requires energy in the form of the electrochemical potential of the inner membrane and ATP. Conversions of energy in mitochondria are disturbed in mitochondrial disorders that affect oxidative phosphorylation. Despite the widely accepted dependence of protein import into mitochondria on mitochondrial bioenergetics, effects of mitochondrial disorders on biogenesis of the mitochondrial proteome are poorly characterized. Here, we describe molecular tools that can be used to explore mitochondrial protein import in intact cells, the mitoRUSH assay, and a novel method based on labeling of nascent proteins with an amino acid analog and click chemistry. Using these orthogonal approaches, we discovered that defects in the electron transport chain and manipulating the expression of TIMM23, as well as the TIMM17A or TIMM17B paralogs, in human cells are associated with a decrease in protein import into mitochondria. We postulate that in the absence of a functional electron transfer chain, the mechanisms that support electrochemical potential of the inner membrane and ATP production are insufficient to sustain the import of proteins to mitochondria.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 13","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

MatriCom, a single-cell RNA-sequencing data mining tool to infer cell-extracellular matrix interactions. MatriCom：一个scRNA-Seq数据挖掘工具，用于推断ECM-ECM和cell-ECM通信系统。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-11 DOI: 10.1242/jcs.263927

Rijuta Lamba, Asia M Paguntalan, Petar B Petrov, Alexandra Naba, Valerio Izzi

{"title":"MatriCom, a single-cell RNA-sequencing data mining tool to infer cell-extracellular matrix interactions.","authors":"Rijuta Lamba, Asia M Paguntalan, Petar B Petrov, Alexandra Naba, Valerio Izzi","doi":"10.1242/jcs.263927","DOIUrl":"10.1242/jcs.263927","url":null,"abstract":"The extracellular matrix (ECM) is a complex meshwork of proteins forming the framework of all multicellular organisms. Protein interactions are critical to building and remodeling the ECM meshwork, while interactions between ECM proteins and their receptors are essential to initiate signal transduction. Here, we present MatriCom, a web application (https://matrinet.shinyapps.io/matricom) and a companion R package, devised to infer communications between ECM components and between different cell populations and the ECM from single-cell RNA-sequencing (scRNA-Seq) datasets. MatriCom relies on a unique database, MatriComDB, of over 25,000 curated interactions involving matrisome components to impute interactions from expression data. MatriCom offers the option to query user-generated or open-access datasets sourced from large sequencing efforts. MatriCom also accounts for specific rules governing ECM protein interactions. We illustrate how MatriCom can generate novel biological insights by building the first human kidney matrisome communication network. Last, applied to a panel of 46 scRNA-Seq datasets of healthy adult tissues, we demonstrate how MatriCom can shed light on the mechanisms of conservation and diversification of ECM assemblies and cell-ECM interactions.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274965","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

Mitochondrial topoisomerases, nucleoid architecture and mtDNA repair in human disease. 人类疾病中的线粒体拓扑异构酶、类核结构和mtDNA修复。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-07-01 Epub Date: 2025-07-07 DOI: 10.1242/jcs.263638

Sangheeta Bhattacharjee, Benu Brata Das

{"title":"Mitochondrial topoisomerases, nucleoid architecture and mtDNA repair in human disease.","authors":"Sangheeta Bhattacharjee, Benu Brata Das","doi":"10.1242/jcs.263638","DOIUrl":"https://doi.org/10.1242/jcs.263638","url":null,"abstract":"DNA topoisomerases are essential for maintaining DNA topology, gene expression and the accurate transmission of genetic information. Mitochondria possess circular DNA (mtDNA), which, unlike nuclear chromosomes, lacks protective histones and exists in nucleoprotein complexes called nucleoids, which are vital for mtDNA stability. Although the mitochondrial genome encodes essential genes involved in ATP production via oxidative phosphorylation, it does not encode crucial mtDNA maintenance genes and depends entirely on nuclear-encoded proteins for mtDNA maintenance. These include nuclear-encoded topoisomerases (i.e. Top1mt, Top2α, Top2β and Top3α), which alleviate topological stress during mtDNA transcription and replication, and mitochondrial transcription factor A (TFAM), are crucial for ensuring proper nucleoid structure and mtDNA packaging. Furthermore, tyrosyl-DNA phosphodiesterase 1 and 2 (TDP1 and TDP2) participate in the repair of mtDNA damage associated with trapped topoisomerase-mtDNA complexes, which can compromise mtDNA integrity and contribute to neurodegeneration, cancer and premature aging. Drugs that stabilize these protein-DNA adducts (PDAs) to induce mtDNA damage and mitochondrial dysfunction are promising new strategies for cancer therapy. This Review explores the essential roles of mitochondrial topoisomerases, overviews mechanisms involved in mtDNA repair and discusses how mitochondrial fission and mitophagy are employed as a survival strategy for clearing damaged mtDNA.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 13","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Transmembrane protein 184B (TMEM184B) modulates endolysosomal acidification via the vesicular proton pump. 跨膜蛋白184B （TMEM184B）通过囊泡质子泵调节内溶酶体酸化。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-30 DOI: 10.1242/jcs.263908

Elizabeth B Wright, Erik G Larsen, Marco Padilla-Rodriguez, Paul R Langlais, Martha R C Bhattacharya

{"title":"Transmembrane protein 184B (TMEM184B) modulates endolysosomal acidification via the vesicular proton pump.","authors":"Elizabeth B Wright, Erik G Larsen, Marco Padilla-Rodriguez, Paul R Langlais, Martha R C Bhattacharya","doi":"10.1242/jcs.263908","DOIUrl":"10.1242/jcs.263908","url":null,"abstract":"Disruption of endolysosomal acidification causes toxic protein accumulation and neuronal dysfunction linked to neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms regulating neuronal endolysosomal pH remain unclear. TMEM184B is a conserved 7-pass transmembrane protein essential for synaptic function, and sequence disruption is associated with neurodevelopmental disorders. Here we identify TMEM184B as a key regulator of endolysosomal acidification. TMEM184B localizes to early and late endosomes, and proteomic analysis confirms that TMEM184B interacts with endosomal proteins, including the vacuolar ATPase (V-ATPase), a multi-subunit proton pump critical for lumenal acidification. Tmem184b-mutant mouse cortical neurons have reduced endolysosomal acidification compared to wild type neurons. We find reductions in V-ATPase complex assembly in Tmem184b-mutant mouse brains, suggesting TMEM184B facilitates endosomal flux by promoting V-ATPase activity. These findings establish TMEM184B as a regulator of neuronal endosomal acidification and provide mechanistic insight into its role in TMEM184B-associated nervous system disorders.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Chemically tunable FOXM1-D sensor revealed FOXM1 direct influence on cell cycle. 化学可调FOXM1- d传感器揭示FOXM1对细胞周期的直接影响。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-30 DOI: 10.1242/jcs.263749

Kriengkrai Phongkitkarun, Porncheera Chusorn, Maliwan Kamkaew, Supawan Jamnongsong, Eric W-F Lam, Chamras Promptmas, Somponnat Sampattavanich

{"title":"Chemically tunable FOXM1-D sensor revealed FOXM1 direct influence on cell cycle.","authors":"Kriengkrai Phongkitkarun, Porncheera Chusorn, Maliwan Kamkaew, Supawan Jamnongsong, Eric W-F Lam, Chamras Promptmas, Somponnat Sampattavanich","doi":"10.1242/jcs.263749","DOIUrl":"https://doi.org/10.1242/jcs.263749","url":null,"abstract":"Forkhead box protein M1 (FOXM1) is a transcription factor required for the G2/M transition and is frequently upregulated in cancers, promoting tumor progression and therapy resistance. However, its dynamic regulation throughout the cell cycle remains unclear. We developed a tunable FOXM1-DHFR (FOXM1-D) sensor in non-malignant MCF10A cells, enabling real-time monitoring and manipulation of FOXM1 levels. Using trimethoprim (TMP) to stabilize FOXM1-D, we quantified its production, degradation, and nuclear translocation during G1 and G2 phases. Overexpression of FOXM1-D accelerated cell division in G1 and S phases but did not affect G2-synchronized cells. Notably, 70%-90% of FOXM1-D overexpressing cells were arrested after the first division, whereas those with timely degradation allowed a second division. Sustained FOXM1-D overexpression induced cell cycle arrest in daughter cells, highlighting the role of FOXM1 kinetics in determining cell fate. Sustained FOXM1-D upregulates p21, triggering G1 arrest. Thus, targeting FOXM1 exploits its dual capacity to induce oncogene-induced senescence (OIS) or suppress mitotic entry. Our study provides a basis for precision therapies that align interventions with FOXM1 kinetics to improve outcomes in FOXM1-driven tumors.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Inhibition of Hedgehog signaling does not mitigate polycystic kidney disease severity in a Pkd1 mutant mouse model. 在Pkd1突变小鼠模型中，抑制刺猬信号传导不能减轻多囊肾病的严重程度。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-23 DOI: 10.1242/jcs.264133

Sean Gombart, Scott Houghtaling, Tzu-Hua Ho, David R Beier

引用次数: 0

A data-driven model for mitochondrial inner membrane remodeling as a driving force of organelle shaping. 线粒体内膜重塑作为细胞器形成驱动力的数据驱动模型。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-15 Epub Date: 2025-06-20 DOI: 10.1242/jcs.263850

Noga Preminger, Ben Zucker, Sarah Hassdenteufel, Till Stephan, Stefan Jakobs, Michael M Kozlov, Maya Schuldiner

{"title":"A data-driven model for mitochondrial inner membrane remodeling as a driving force of organelle shaping.","authors":"Noga Preminger, Ben Zucker, Sarah Hassdenteufel, Till Stephan, Stefan Jakobs, Michael M Kozlov, Maya Schuldiner","doi":"10.1242/jcs.263850","DOIUrl":"10.1242/jcs.263850","url":null,"abstract":"Mitochondria are dynamic organelles exhibiting diverse shapes. Although variation in mitochondrial shapes, which range from spheres to elongated tubules, and the transitions between them are clearly seen in many cell types, the molecular mechanisms governing this morphological variability remain poorly understood. Here, we propose a biophysical model for the shape transition between spheres and tubules based on the interplay between the inner and outer mitochondrial membranes. Our model suggests that the difference in surface area, arising from folding of the inner membrane into cristae, correlates with mitochondrial elongation. Analysis of live-cell super-resolution microscopy data supports this correlation, linking elongated shapes to the extent of cristae in the inner membrane. Knocking down cristae-shaping proteins further confirms the impact on mitochondrial shape, demonstrating that defects in cristae formation correlate with mitochondrial sphericity. Our results suggest that the dynamics of the inner mitochondrial membrane are not only important for simply creating surface area required for respiratory capacity but go beyond that to affect the whole organelle morphology. This work explores the biophysical foundations that govern the shape of individual mitochondria, suggesting potential links between mitochondrial structure and function. This should be of profound significance, particularly in the context of disrupted cristae-shaping proteins and their implications in mitochondrial diseases.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078313","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

Phagocytosis at a glance. 吞噬作用一目了然。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-15 Epub Date: 2025-07-01 DOI: 10.1242/jcs.263833

Manon Depierre, Chiara Pompili, Florence Niedergang

引用次数: 0

SLC-25A46 regulates mitochondrial fusion through the mitofusin protein FZO-1 and is essential for maintaining neuronal morphology. SLC-25A46通过FZO-1/Mitofusin调控线粒体融合。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-15 Epub Date: 2025-06-23 DOI: 10.1242/jcs.263571

Hiroyuki Obinata, Taisei Watanabe, Hironori Takahashi, Satoshi Shimo, Toshiyuki Oda, Asako Sugimoto, Shinsuke Niwa

{"title":"SLC-25A46 regulates mitochondrial fusion through the mitofusin protein FZO-1 and is essential for maintaining neuronal morphology.","authors":"Hiroyuki Obinata, Taisei Watanabe, Hironori Takahashi, Satoshi Shimo, Toshiyuki Oda, Asako Sugimoto, Shinsuke Niwa","doi":"10.1242/jcs.263571","DOIUrl":"10.1242/jcs.263571","url":null,"abstract":"Mitochondria are dynamic organelles shaped by sequential fission and fusion events. The mitochondrial protein SLC25A46 has been identified as a causative gene for mitochondrial neuropathies. However, the function of SLC25A46 in mitochondrial morphogenesis remains controversial, with several reports suggesting it acts as a mitochondrial fission factor, whereas others propose it as a fusion factor. In this study, employing forward genetics, we identified slc-25A46, a Caenorhabditis elegans ortholog of human SLC25A46, as an essential factor for mitochondrial fusion. Suppressor mutagenesis screening revealed loss-of-function mutations in drp-1, a mitochondrial fission factor, as suppressors of slc-25A46. The phenotype of slc-25A46 mutants is similar to that of mutants in the worm mitofusin ortholog fzo-1, wherein the mitochondrial fusion factor is disrupted. Overexpressing FZO-1 mitigated mitochondrial defects in slc-25a46 mutants, indicating that SLC-25A46 promotes fusion through FZO-1. Disease model worms carrying mutations associated with SLC25A46 exhibited mitochondrial fragmentation and accelerated neurodegeneration, suggesting that slc-25A46 maintains neuronal morphology through regulating mitochondrial fusion regulation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180143","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

In vitro reconstitution of a minimal human centrosome scaffold capable of forming and clustering microtubule asters. 能够形成和聚集微管紫菀的最小人类中心体支架的体外重建。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-06-15 Epub Date: 2025-06-27 DOI: 10.1242/jcs.264121

Manolo U Rios, Weronika E Stachera, Nicole E Familiari, Claudia Brito, Thomas Surrey, Jeffrey B Woodruff

{"title":"In vitro reconstitution of a minimal human centrosome scaffold capable of forming and clustering microtubule asters.","authors":"Manolo U Rios, Weronika E Stachera, Nicole E Familiari, Claudia Brito, Thomas Surrey, Jeffrey B Woodruff","doi":"10.1242/jcs.264121","DOIUrl":"10.1242/jcs.264121","url":null,"abstract":"CDK5RAP2 (also known as CEP215) is a key pericentriolar material (PCM) protein that recruits microtubule-nucleating factors at human centrosomes. Here, using an in vitro reconstitution system, we show that CDK5RAP2 is sufficient to form micron-scale scaffolds using nanometer-scale nucleators in a PLK-1-regulated manner. CDK5RAP2 assemblies recruited and activated γ-tubulin ring complexes (γ-TuRCs) which, in the presence of α/β-tubulin, generated microtubule asters. We found that amino acid F75 in CDK5RAP2 helps to recruit γ-TuRC and is indispensable for γ-TuRC activation. Furthermore, our system recapitulated key features of centrosome-amplified cancer cells. CDK5RAP2 scaffolds recruited the molecular motor HSET (also known as KifC1), which enhanced concentration of α/β-tubulin, microtubule polymerization and clustering of the assemblies. Our results highlight the specificity and selectivity of in vitro-generated CDK5RAP2 scaffolds, and identify a minimal set of components required for human PCM assembly and function. This minimal model offers a powerful tool for studying centrosome biology and dysfunction in human health and disease.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199238","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