Journal of Cell Biology最新文献_第8页

Design principles of human membrane protein topology. 人体膜蛋白拓扑结构设计原理。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-05-29 DOI: 10.1083/jcb.202604059

Haoxi Wu, Ramanujan S Hegde

引用次数: 0

Mitochondria limit coenzyme Q export under cholesterol biosynthetic stress. 胆固醇生物合成应激下线粒体限制辅酶Q的输出。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-08 DOI: 10.1083/jcb.202507174

Marjana Ndoci, Sharanya Bhattacharya, Ishita Agrawal, Yvonne Hinze, Kathrin Lemke, Anna-Lena Schumacher, Esther Uijttewaal, Ulrich Elling, Steffen Lawo, Patrick Giavalisco, Thomas Langer, Soni Deshwal

{"title":"Mitochondria limit coenzyme Q export under cholesterol biosynthetic stress.","authors":"Marjana Ndoci, Sharanya Bhattacharya, Ishita Agrawal, Yvonne Hinze, Kathrin Lemke, Anna-Lena Schumacher, Esther Uijttewaal, Ulrich Elling, Steffen Lawo, Patrick Giavalisco, Thomas Langer, Soni Deshwal","doi":"10.1083/jcb.202507174","DOIUrl":"10.1083/jcb.202507174","url":null,"abstract":"Coenzyme Q (CoQ) is a hydrophobic lipid primarily synthesized in the mitochondria, though it is also present in non-mitochondrial membranes. However, the metabolic pathways that regulate intracellular CoQ distribution are unknown. This study identifies a key role for the mevalonate pathway in regulating CoQ distribution. The mevalonate pathway synthesizes isopentenyl pyrophosphate (IPP) as the precursor metabolite for both CoQ and cholesterol. We show that CoQ synthesis remains stable regardless of whether the mevalonate pathway is upregulated or downregulated. Upregulation of HMG-CoA reductase (HMGCR), indicative of increased mevalonate flux, enhances cholesterol ester synthesis without altering CoQ levels. When the pathway is downregulated, cholesterol synthesis declines, yet mitochondrial CoQ levels are preserved. Under these limiting conditions, mitochondria reduce CoQ export to maintain their internal CoQ pool. While this adaptation sustains mitochondrial respiration, it diminishes extramitochondrial CoQ availability and sensitizes cells to ferroptosis. These findings uncover a mitochondria-driven mechanism that preserves respiratory function by prioritizing CoQ retention during metabolic stress.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13245278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Opposing actomyosin pools establish epithelial polarity during naive pluripotency exit. 相反的肌动球蛋白池在初始多能性退出期间建立上皮极性。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-02 DOI: 10.1083/jcb.202408198

Yu Shi, Nadia I Manzi, Nicole R Grater, Nitya Kopparapu, Lauren S Ohler, Bailey N de Jesus, Daniel J Dickinson

{"title":"Opposing actomyosin pools establish epithelial polarity during naive pluripotency exit.","authors":"Yu Shi, Nadia I Manzi, Nicole R Grater, Nitya Kopparapu, Lauren S Ohler, Bailey N de Jesus, Daniel J Dickinson","doi":"10.1083/jcb.202408198","DOIUrl":"10.1083/jcb.202408198","url":null,"abstract":"Epithelial cell polarity is fundamental for embryonic development and organ function. During organogenesis, epithelia often develop from unpolarized precursor cells. How mammalian epithelial cells establish polarity de novo is unclear, in part due to challenges of observing this process in real time in nontransformed cells. Here, we leverage 3D spheroid culture of mouse embryonic stem cells, fluorescent protein knock-in, and live imaging to study epithelial polarity establishment. We show that apical myosin activity, regulated by myosin light chain kinase (MLCK), is crucial for proper epithelial polarity in this system. MLCK-dependent actin flows carry ZO-1, a tight junction component, to the apical junction. A second pool of myosin, regulated by Rho kinase, localizes basally and modulates ZO-1 recruitment to the membrane. MLCK inhibition also disrupts localization of atypical protein kinase C and podocalyxin, supporting a broader role of MLCK-dependent myosin in establishing the apical membrane. Our results support a model in which distinct apical and basal actomyosin pools coordinate epithelial polarity establishment.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Centriolar satellites assemble via a hierarchical pathway driven by PCM1 multimerization. 向心卫星通过PCM1多聚化驱动的分层路径组装。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-11 DOI: 10.1083/jcb.202509238

Efe Begar, Ece Seyrek, Selin Yilmaz-Karaoglu, Melis D Arslanhan, Ezgi Odabasi, Elif Nur Firat-Karalar

{"title":"Centriolar satellites assemble via a hierarchical pathway driven by PCM1 multimerization.","authors":"Efe Begar, Ece Seyrek, Selin Yilmaz-Karaoglu, Melis D Arslanhan, Ezgi Odabasi, Elif Nur Firat-Karalar","doi":"10.1083/jcb.202509238","DOIUrl":"10.1083/jcb.202509238","url":null,"abstract":"Centriolar satellites (CS) are ubiquitous membraneless organelles with diverse functions and links to developmental and neuronal diseases. However, the molecular principles governing their assembly and regulation remain poorly understood. To address this, we developed cellular and in vitro biogenesis assays that enable spatiotemporal quantification of CS granule properties during assembly, remodeling, and maintenance. Using these tools, we show that CS assemble via a hierarchical pathway initiated by pericentriolar material-1 (PCM1) scaffold formation and followed by client recruitment. PCM1 intrinsically assembles into granules through multimerization, a process modulated by the cytoskeleton. High-resolution imaging revealed that PCM1 and its clients occupy distinct subdomains with different compositions and dynamics. Perturbing PCM1 multimerization impaired ciliary signaling and mitotic progression, underscoring its functional importance. Together, these findings define the molecular basis of CS biogenesis, establish tools to probe CS regulation, and provide a framework for understanding how CS deregulation contributes to disease. More broadly, these may extend to other membraneless organelles and help explain their specificity and plasticity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The Rab GEF VINE couples phosphatase recruitment to GAP-mediated Rab5 inactivation. Rab GEF VINE将磷酸酶募集与gap介导的Rab5失活结合起来。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-07-07 DOI: 10.1083/jcb.202601107

Mia S Frier, Shawn P Shortill, Michael Davey, Elizabeth Conibear

{"title":"The Rab GEF VINE couples phosphatase recruitment to GAP-mediated Rab5 inactivation.","authors":"Mia S Frier, Shawn P Shortill, Michael Davey, Elizabeth Conibear","doi":"10.1083/jcb.202601107","DOIUrl":"10.1083/jcb.202601107","url":null,"abstract":"Rab5-family GTPases cycle between active and inactive forms to regulate endosomal membrane identity and protein trafficking. VPS9-family guanine nucleotide exchange factors (GEFs) promote Rab activation at endosomes, whereas GTPase-activating proteins (GAPs) oppose Rab signaling. Here, we identify an unexpected role for the yeast VPS9-family GEF complex VINE in promoting the inactivation of the Rab5 homolog Vps21. Through genome-wide proximity screening, predictive modeling, targeted mutagenesis, and in vivo assays, we show that VINE recruits the protein phosphatase Glc7 through the ankyrin repeat-containing domain of its GEF subunit Vrl1. Our results suggest this directs the dephosphorylation of Kxd1, a subunit of the GAP adaptor BLOC-1, which in turn enhances its interaction with the Vps21-specific GAP Msb3 and accelerates GAP-mediated Vps21 inactivation. Thus, VINE is a VPS9-family GEF complex that selectively limits endosomal Rab signaling. These findings reveal a novel mechanism integrating positive and negative Rab regulation, providing insight into how Rab5 signaling is fine-tuned during endosomal trafficking and maturation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Asymmetric mitochondrial trafficking balances perinuclear biogenesis to maintain network morphology. 不对称线粒体运输平衡核周围生物发生，维持网络形态。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-03 DOI: 10.1083/jcb.202409118

Julius Winter, Juan C Landoni, Keaton B Holt, Sheda Ben Nejma, Emine Berna Durmus, Tatjana Kleele, Elena F Koslover, Suliana Manley

{"title":"Asymmetric mitochondrial trafficking balances perinuclear biogenesis to maintain network morphology.","authors":"Julius Winter, Juan C Landoni, Keaton B Holt, Sheda Ben Nejma, Emine Berna Durmus, Tatjana Kleele, Elena F Koslover, Suliana Manley","doi":"10.1083/jcb.202409118","DOIUrl":"10.1083/jcb.202409118","url":null,"abstract":"In functionally polarized cells, mitochondria can form distinct subpopulations, positioned at sites of varying metabolic and energetic demands. Thus far, the potential presence of such subpopulations and implications of their intracellular trafficking in immobile and proliferative cells remain largely undescribed, despite such cells serving as key models. Here, we use substrate micropatterning to create reproducible morphologies of cultured immortalized cells, enabling us to define mitochondrial subpopulations and follow their trafficking by photoactivation. We discovered that mitochondrial material is dispersed asymmetrically throughout the cell via biased anterograde transport from the perinuclear area. Combining quantitative analysis and in silico modeling, we characterize the causes and consequences of unbalanced mitochondrial trafficking. Our findings indicate that this bias is required to distribute new material resulting from perinuclear mitochondrial biosynthesis to sustain mitochondrial mass distribution across the cell and to maintain normal network connectivity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Met-Vision reveals coexisting energetic states in tissue macrophages redistributed by inflammation. Met-Vision揭示了炎症重新分配的组织巨噬细胞共存的能量状态。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-12 DOI: 10.1083/jcb.202603170

Adriana Lecourieux, Margot Bardou, Zacarias Garcia, Philippe Bousso

{"title":"Met-Vision reveals coexisting energetic states in tissue macrophages redistributed by inflammation.","authors":"Adriana Lecourieux, Margot Bardou, Zacarias Garcia, Philippe Bousso","doi":"10.1083/jcb.202603170","DOIUrl":"10.1083/jcb.202603170","url":null,"abstract":"The function of tissue-associated macrophages is tightly linked to their energy metabolism. Yet, the diversity of macrophage metabolic profiles coexisting in tissues at homeostasis or during immune challenges is incompletely understood. Here, we introduce Met-Vision, an imaging-based pipeline for single-cell functional profiling and classification of energy metabolism. Across multiple tissue contexts, we identified that macrophages do not adopt a uniform metabolic profile but typically coexist in four discrete metabolic states with distinct dependence on OXPHOS and metabolic plasticity. Inflammation reconfigured the distribution of macrophage metabolic profiles that remained heterogeneous. Notably, inflammation-derived nitric oxide finely tuned the distribution of macrophage energetic states. These findings challenge the view of homogeneous metabolic activation and reveal a layer of metabolic diversity in tissue at steady state and during inflammation. The ability to stratify macrophage energy metabolic profiles with Met-Vision should help guide the development of metabolism-targeted therapies for inflammatory diseases, cancer, and metabolic disorders.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Synergistic assembly, disassembly, and protection of complex forms of bundled F-actin. 结合的f -肌动蛋白复合形式的协同组装、拆卸和保护。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-07-01 DOI: 10.1083/jcb.202509039

Sudeepa Rajan, Jimok Yoon, Heng Wu, Raju Baskar, Roman Aguirre, Jonathan R Terman, Emil Reisler

{"title":"Synergistic assembly, disassembly, and protection of complex forms of bundled F-actin.","authors":"Sudeepa Rajan, Jimok Yoon, Heng Wu, Raju Baskar, Roman Aguirre, Jonathan R Terman, Emil Reisler","doi":"10.1083/jcb.202509039","DOIUrl":"10.1083/jcb.202509039","url":null,"abstract":"Actin's transition from monomers (G-actin) to polymers (F-actin) and then into bundled and branched networks underlies many cellular and system functions. Yet, how these networks are dynamically assembled and disassembled is incompletely understood-including why F-actin is often simultaneously and redundantly bundled by different proteins. Here, we focus on fascin and espin, two bundlers that often coexist and robustly bundle F-actin. We find that they synergistically bundle F-actin compared to equal amounts of each one alone. However, we show that bundles containing these two proteins are robustly destabilized by a synergism between Mical and cofilin, indicating mechanisms of how complex bundles are disassembled and remodeled. Yet, our results also reveal that together fascin and espin protect F-actin from this disassembly more effectively than each one alone-including to regulate F-actin disassembly and cellular remodeling in vivo. These findings reveal mechanisms for assembling and disassembling complex networks of bundled F-actin, including a synergism between different bundlers and disassemblers in these processes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13322139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

E- and N-cadherin drive hepatic polarity and lumen elongation via opposing effects on RhoA activity. E-钙粘蛋白和n -钙粘蛋白通过对RhoA活性的相反作用来驱动肝极性和管腔伸长。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-05-27 DOI: 10.1083/jcb.202509170

Junya Hayase, Li Yang, Yu-Heng Zhou, Kangji Wang, Cheng-Ran Xu, Erfei Bi

{"title":"E- and N-cadherin drive hepatic polarity and lumen elongation via opposing effects on RhoA activity.","authors":"Junya Hayase, Li Yang, Yu-Heng Zhou, Kangji Wang, Cheng-Ran Xu, Erfei Bi","doi":"10.1083/jcb.202509170","DOIUrl":"10.1083/jcb.202509170","url":null,"abstract":"Hepatocytes display a unique polarity, forming narrow apical tubes-bile canaliculi (BCs)-between adjacent cells that are essential for liver function. Unlike most epithelial cells, hepatocytes express both E- and N-cadherin, yet their specific roles during BC tubulogenesis remain incompletely understood. Here, we show that these cadherins are collectively required for hepatic polarity and BC formation yet act through distinct mechanisms. E-cadherin localizes to adherens junctions, lateral membranes, and the cleavage furrow, where it promotes division-linked BC elongation and cell-cell contact formation by controlling spindle orientation and RhoA activation via NuMA and ARHGEF17. In contrast, N-cadherin is restricted to adherens junctions and maintains hepatic polarity by attenuating RhoA activity through the p120-catenin family member ARVCF and its partner p190B/ARHGAP5. Together, these findings reveal that dual cadherin expression drives hepatic polarity and BC formation by controlling RhoA activity in a coordinated yet opposing manner.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

A cytosolic IF1 reporter enables real-time visualization of severe mitochondrial membrane damage. 胞质IF1报告细胞能够实时显示严重的线粒体膜损伤。

IF 6.1 1区生物学

Journal of Cell Biology Pub Date : 2026-08-03 Epub Date: 2026-06-02 DOI: 10.1083/jcb.202511088

Erqing Gao, Liwei Guan, Kehang Zhang, Shuze Qi, Jingxiu Xu, Jie Zhang, Tianyi Zhu, Bing Yang, Chonglin Yang, Eric Miska, Mao Zhang, Suhong Xu

{"title":"A cytosolic IF1 reporter enables real-time visualization of severe mitochondrial membrane damage.","authors":"Erqing Gao, Liwei Guan, Kehang Zhang, Shuze Qi, Jingxiu Xu, Jie Zhang, Tianyi Zhu, Bing Yang, Chonglin Yang, Eric Miska, Mao Zhang, Suhong Xu","doi":"10.1083/jcb.202511088","DOIUrl":"10.1083/jcb.202511088","url":null,"abstract":"Maintenance of mitochondrial integrity is fundamental for cellular survival, yet how cells recognize catastrophic mitochondrial membrane damage remains unknown. Here, we identify MAI-1 as the first genetically encoded reporter of severe mitochondrial membrane damage. MAI-1 is a Caenorhabditis elegans homolog of the ATP synthase inhibitor IF1 that lacks a mitochondrial targeting sequence, resides in the cytosol under basal conditions, but rapidly and irreversibly translocates to severely damaged mitochondria within milliseconds. We validate MAI-1 across diverse injury paradigms and demonstrate that cytosolic IF1 variants from other species exhibit conserved damage-induced recruitment. Mechanistically, MAI-1 recruitment requires the presence of an intact ATP synthase complex. Using MAI-1 as a sensor, we uncover that these severely damaged mitochondria are cleared through the LGG-1-mediated, PINK1/PARKIN-independent lysosomal pathway. Together, our findings establish a powerful tool for visualizing severe mitochondrial membrane damage and reveal a surveillance mechanism dedicated to structural integrity control.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 8","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13228541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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