Nature Cell Biology最新文献

{"title":"Grow up, beta cells","authors":"Angela R. Parrish","doi":"10.1038/s41556-025-01705-x","DOIUrl":"https://doi.org/10.1038/s41556-025-01705-x","url":null,"abstract":"<p>Mitochondrial impairment, particularly in beta cells, is closely associated with metabolic disorders such as type 2 diabetes (T2D). In a recent paper, Walker et al. demonstrate that integrated stress response (ISR) signalling from the mitochondria to the nucleus leads to dedifferentiation and loss of maturity in beta cells, causing glucose intolerance and defects in insulin secretion.</p><p>To determine the role of mitochondrial dysfunction in T2D, the authors generated beta cell-specific mouse models with abnormalities in mitochondrial quality control and observed accompanying metabolic dysfunction. Transcriptomic analysis of islets showed changes in expression of cell maturity markers, suggesting acquisition of cellular immaturity, and induction of the ISR. Single-nucleus experiments demonstrate loss of chromatin accessibility at terminal identity genes. Finally, the authors show that small-molecule inhibition of the ISR alleviates the loss of beta cell mass and glucose intolerance caused by mitochondrial impairment.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"145 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312029","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}

{"title":"Light microscopy reporting for reproducibility","authors":"","doi":"10.1038/s41556-025-01704-y","DOIUrl":"https://doi.org/10.1038/s41556-025-01704-y","url":null,"abstract":"We announce a cross-journal pilot at Nature Portfolio journals with a goal of implementing standardized light and fluorescence microscopy reporting to improve methodological description and aid in reproducibility efforts.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"12 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312250","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}

{"title":"Cytoplasmic control of spindle architecture","authors":"Gabriel Cavin-Meza, Rebecca Heald","doi":"10.1038/s41556-025-01686-x","DOIUrl":"https://doi.org/10.1038/s41556-025-01686-x","url":null,"abstract":"Dense crowding of macromolecules in the cytoplasm is a fundamental property of cells. A study now identifies a pathway by which cytoplasmic dilution in differentiating neurons alters the morphology of the cell division apparatus, which likely contributes to proper neurodevelopment.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"34 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304458","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}

{"title":"Synergy between microtubule and actin networks in centrosome positioning","authors":"Petra Gross","doi":"10.1038/s41556-025-01699-6","DOIUrl":"https://doi.org/10.1038/s41556-025-01699-6","url":null,"abstract":"<p>Centrosome positioning is important for cellular function, but the exact forces and spatial distribution that underly accurate centrosome centring in adherent cells remain unclear.</p><p>To assess the contribution of pushing and pulling forces exerted by microtubules to centrosome positioning, Manuel Théry and colleagues used laser ablation to investigate the effects of microtubule disruption. They observed that the microtubule and actin networks are closely connected as any centrosome recoil in response to microtubule ablation also results in a similar relaxation of surrounding actin filaments, indicating that microtubules are unable to generate the forces necessary to drive centrosome motion. Instead, the authors demonstrate that the actomyosin network creates a centripetal flow that drags the centrosome near the centre in adherent cells, and dynein-based transport along the microtubules is involved in the redistribution of cell mass around the centrosome to maintain the centrosomal position.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"626 1","pages":"878"},"PeriodicalIF":21.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312027","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}

{"title":"Surveilling ribosome biogenesis","authors":"Daryl J. V. David","doi":"10.1038/s41556-025-01700-2","DOIUrl":"https://doi.org/10.1038/s41556-025-01700-2","url":null,"abstract":"<p>Eukaryotic ribosomal quality control degrades faulty ribosomal assemblies, but precise mechanisms to target defective pre-ribosomes remain unclear. Now, Akers et al. report a ribosome assembly surveillance pathway that requires the protein ZNF574.</p><p>Using the K562 lymphoblast human cell line, the authors find that mutant ribosomal protein uL16^mut blocks 60S ribosome maturation; these 60S^mut defective subunits are degraded during biogenesis by the ubiquitin proteasome system. Using a CRISPR interference screen, the authors identified ZNF574, predicted to interact with ribosomal proteins, as required for 60S^mut degradation. ZNF574–uL16 interactions were assessed with co-immunoprecipitation and proximity ligation assays. Cryo-electron microscopy of 60S^mut suggests that the peptidyl transferase centre adopts a mature conformation. The authors propose that 60S^mut cannot release eIF6 as the otherwise final step of 60S maturation. ZNF574 depletion stabilizes ribosome mutants with slowed ribosome biogenesis, which suggests that ZNF574 targets stalled biogenesis intermediates. The authors found <i>znf574</i>^−/− homozygous mutant zebrafish embryos display several morphological defects reminiscent of ribosomopathies.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"44 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312028","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}

{"title":"Shaping the composition of the mitochondrial outer membrane","authors":"Gayathri Muthukumar, Jonathan S. Weissman","doi":"10.1038/s41556-025-01683-0","DOIUrl":"https://doi.org/10.1038/s41556-025-01683-0","url":null,"abstract":"<p>Mitochondria are critical double-membraned organelles that act as biosynthetic and bioenergetic cellular factories, with the outer membrane providing an interface with the rest of the cell. Mitochondrial outer membrane proteins regulate a variety of processes, including metabolism, innate immunity and apoptosis. Although the biophysical and functional diversity of these proteins is highly documented, the mechanisms of their biogenesis and the integration of that into cellular homeostasis are just starting to take shape. Here, focusing on α-helical outer membrane proteins, we review recent insights into the mechanisms of synthesis and cytosolic chaperoning, insertion and assembly in the lipid bilayer, and quality control of unassembled or mislocalized transmembrane domains. We further discuss the role convergent evolution played in this process, comparing key biogenesis players from lower eukaryotes, including yeast and trypanosomes, with multicellular metazoan systems, and draw comparisons with the endoplasmic reticulum biogenesis system, in which membrane proteins face similar challenges.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"13 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296151","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}

{"title":"ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome","authors":"Thomas L. Clarke, Hyo Min Cho, Ilaria Ceppi, Boya Gao, Tribhuwan Yadav, Giorgia G. Silveira, Ruben Boon, Barbara Martinez-Pastor, Nana Yaa A. Amoh, Belen Machin, Tiziano Bernasocchi, Dua Ashfaq, Josefina Mendez, Zeeba Kamaliyan, José Del Río Pantoja, Giuliana Sardi Rogines, Blaine T. Crowley, Daniel E. McGinn, Victoria Giunta, Oanh Tran, Elaine H. Zackai, Li Lan, Lee Zou, Beverly S. Emanuel, Donna M. McDonald-McGinn, Petr Cejka, Raul Mostoslavsky","doi":"10.1038/s41556-025-01674-1","DOIUrl":"https://doi.org/10.1038/s41556-025-01674-1","url":null,"abstract":"<p>DNA double-strand breaks (DSB) are among the most deleterious forms of DNA damage and, if unresolved, result in DNA mutations and chromosomal aberrations that can cause disease, including cancer. Repair of DSBs by homologous recombination requires extensive nucleolytic digestion of DNA ends in a process known as DNA-end resection. In recent years, progress has been made in understanding how this process is initiated, but the later stages of this process—long-range DNA-end resection—are not well understood. Many questions remain in terms of how the DNA helicases and endonucleases that catalyse this process are regulated, a key step to avoiding spurious activity in the absence of breaks. The importance of DNA-end resection in human disease is highlighted by several human genetic syndromes that are caused by mutations or deficiencies in key proteins involved in this process. Here, using high-throughput microscopy coupled with a cDNA ‘chromORFeome’ library, we identified ZNF280A as an uncharacterized chromatin factor that is recruited to breaks and essential for DNA DSB repair. Lack of ZNF280A drives genomic instability and substantial sensitivity to DNA-damaging agents. Mechanistically, we demonstrate that ZNF280A promotes long-range DNA-end resection by facilitating the recruitment of the BLM–DNA2 helicase–nuclease complex to DNA DSB sites, enhancing efficiency of the enzymatic activity of this complex at DNA damage sites. ZNF280A is therefore essential for DNA-end resection and DNA repair by homologous recombination. Importantly, ZNF280A is hemizygously deleted in a human genetic condition, 22q11.2 distal deletion syndrome. Features of this condition include congenital heart disease, microcephaly, immune deficiency, developmental delay and cognitive deficits—features that are associated with other human syndromes caused by defects in genes involved in DNA repair. Remarkably, cells from individuals with a 22q11.2 distal deletion have defects in DNA-end resection and homologous recombination, resulting in increased incidence of genomic instability. These phenotypes are rescued by reintroduction of ZNF280A, providing evidence of defective DNA repair as a potential mechanistic explanation for several clinical features associated with this human condition.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"1 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296152","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}

{"title":"Cell state-specific cytoplasmic density controls spindle architecture and scaling","authors":"Tobias Kletter, Omar Muñoz, Sebastian Reusch, Abin Biswas, Aliaksandr Halavatyi, Beate Neumann, Benno Kuropka, Vasily Zaburdaev, Simone Reber","doi":"10.1038/s41556-025-01678-x","DOIUrl":"https://doi.org/10.1038/s41556-025-01678-x","url":null,"abstract":"<p>Mitotic spindles are dynamically intertwined with the cytoplasm they assemble in. How the physicochemical properties of the cytoplasm affect spindle architecture and size remains largely unknown. Using quantitative biochemistry in combination with adaptive feedback microscopy, we investigated mitotic cell and spindle morphology during neural differentiation of embryonic stem cells. While tubulin biochemistry and microtubule dynamics remained unchanged, spindles changed their scaling behaviour; in differentiating cells, spindles were considerably smaller than those in equally sized undifferentiated stem cells. Integrating quantitative phase imaging, biophysical perturbations and theory, we found that as cells differentiated, their cytoplasm became more dilute. The concomitant decrease in free tubulin activated CPAP (centrosomal P4.1-associated protein) to enhance the centrosomal nucleation capacity. As a consequence, in differentiating cells, microtubule mass shifted towards spindle poles at the expense of the spindle bulk, explaining the differentiation-associated switch in spindle architecture. This study shows that cell state-specific cytoplasmic density tunes mitotic spindle architecture. Thus, we reveal physical properties of the cytoplasm as a major determinant in organelle size control.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"7 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278754","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}

{"title":"Endoplasmic reticulum–mitochondria contacts are prime hotspots of phospholipid peroxidation driving ferroptosis","authors":"Maria Livia Sassano, Yulia Y. Tyurina, Antigoni Diometzidou, Ellen Vervoort, Vladimir A. Tyurin, Sanket More, Rita La Rovere, Francesca Giordano, Geert Bultynck, Benjamin Pavie, Johan V. Swinnen, Hülya Bayir, Valerian E. Kagan, Luca Scorrano, Patrizia Agostinis","doi":"10.1038/s41556-025-01668-z","DOIUrl":"https://doi.org/10.1038/s41556-025-01668-z","url":null,"abstract":"<p>The peroxidation of membrane phospholipids (PLs) is a hallmark of ferroptosis. The endoplasmic reticulum and mitochondria have been implicated in ferroptosis, but whether intracellular PL peroxidation ensues at their contact sites (endoplasmic reticulum–mitochondria contact sites, EMCSs) is unknown. Using super-resolution live imaging, we charted the spatiotemporal events triggered by ferroptosis at the interorganelle level. Here we show that EMCSs expand minutes after localized PL peroxides are formed and secondarily spread to mitochondria, promoting mitochondrial reactive oxygen species and fission. Oxidative lipidomics unravels that EMCSs host distinct proferroptotic polyunsaturated-PLs, including doubly proferroptotic polyunsaturated-acylated PLs, demonstrating their high propensity to undergo PL peroxidation. Endoplasmic reticulum–mitochondria untethering blunts PL peroxidation and ferroptosis, while EMCS stabilization enhances them. Consistently, distancing EMCSs protects the ferroptosis-susceptible triple-negative breast cancer subtype, harbouring high EMCS-related gene expression and basal PL peroxide levels. Conversely, in insensitive triple-negative breast cancer subtypes, bolstering EMCSs sensitizes them to ferroptosis. Our data unveil endoplasmic reticulum–mitochondria appositions as initial hubs of PL peroxide formation and posit that empowering EMCSs endorses ferroptosis in cancer cells.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"91 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278520","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}

{"title":"A checklist for designing and improving the visualization of scientific data","authors":"Helena Klara Jambor","doi":"10.1038/s41556-025-01684-z","DOIUrl":"https://doi.org/10.1038/s41556-025-01684-z","url":null,"abstract":"Creating clear and engaging scientific figures is crucial to communicate complex data. In this Comment, I condense principles from design, visual perception and data visualization research in a checklist that can help researchers to improve their data visualization, by focusing on clarity, accessibility and design best practices.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278519","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}