{"title":"A redox–auxin connection in response to water deficit","authors":"Kim Baumann","doi":"10.1038/s41580-025-00875-8","DOIUrl":"https://doi.org/10.1038/s41580-025-00875-8","url":null,"abstract":"Reactive oxygen species (ROS) induce the multimerization of Aux/IAA transcriptional repressors, and this ROS–auxin signalling connection functions as a rapid adaptive response to water deficit, inducing a temporary stop in root growth.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"2 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578395","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":"Molecular machineries and pathways of mitochondrial protein transport","authors":"Toshiya Endo, Nils Wiedemann","doi":"10.1038/s41580-025-00865-w","DOIUrl":"https://doi.org/10.1038/s41580-025-00865-w","url":null,"abstract":"<p>Mitochondria contain about 1,000–1,500 different proteins, most of which are encoded by the nuclear genome and synthesized in the cytosol, although a handful are specified by the mitochondrial DNA and translated within mitochondria. The coordinated transport of nucleus-encoded proteins into mitochondria, followed by their proper folding, assembly and/or integration into mitochondrial membranes, is central to mitochondrial biogenesis. In this Review, we describe the pathways and machineries for protein transport across and insertion into the inner and outer mitochondrial membranes, as well as the targeting and sorting signals, and energy requirements for these processes. These machineries include the TOM and SAM complexes in the outer membrane and the TIM complexes in the inner membrane, and some components in the intermembrane space. We emphasize recent developments in our understanding of the protein structures of the transport machineries and discuss mechanisms for the shift of protein localization and correction of mislocalization.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"104 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546987","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}
Manuel Beltrán-Visiedo, Ruth Soler-Agesta, Kristopher A. Sarosiek, Douglas R. Green, Lorenzo Galluzzi
{"title":"Regulation of inflammatory processes by caspases","authors":"Manuel Beltrán-Visiedo, Ruth Soler-Agesta, Kristopher A. Sarosiek, Douglas R. Green, Lorenzo Galluzzi","doi":"10.1038/s41580-025-00869-6","DOIUrl":"https://doi.org/10.1038/s41580-025-00869-6","url":null,"abstract":"<p>Historically, mammalian caspases (a group of cysteine proteases) have been catalogued into two main families based on major biological function: inflammatory caspases and apoptotic caspases. Accumulating evidence from preclinical models, however, argues against such a clearcut distinction, for two main reasons. First, at least in mammals, apoptotic caspases are generally dispensable for cells to succumb to apoptotic stimuli but instead regulate the kinetic and microenvironmental manifestations of the cellular demise in the context of a complex interplay with other cell death pathways. Second, most (if not all) mammalian caspases have evolved into positive or negative regulators of inflammatory processes, either directly or via their ability to control apoptotic and non-apoptotic cell death modalities. Here we discuss the molecular mechanisms through which mammalian caspases regulate inflammation, with emphasis on the ability of apoptotic caspases to suppress inflammatory responses in support of preserved organismal homeostasis.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"70 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533895","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}
İbrahim Avşar Ilık, Xu Yang, ZZ Zhao Zhang, Tuğçe Aktaş
{"title":"Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease","authors":"İbrahim Avşar Ilık, Xu Yang, ZZ Zhao Zhang, Tuğçe Aktaş","doi":"10.1038/s41580-025-00867-8","DOIUrl":"https://doi.org/10.1038/s41580-025-00867-8","url":null,"abstract":"<p>Nearly half of the genome of humans and other mammals consists of transposable elements (TEs). Recent advancements in sequencing technologies have revealed that TEs have important regulatory functions, echoing Barbara McClintock’s 1950s vision of TEs as ‘controlling elements’. Nevertheless, TEs can still interfere with gene expression and are linked to various human diseases. In this Review, we first discuss the multilayered transcriptional and post-transcriptional defence mechanisms that repress TE activity, and examine how they regulate endogenous gene expression. We then discuss recent studies showing that TEs can escape these repression mechanisms and unexpectedly become a vital part of animal development. Finally, we explore findings on TE derepression in cancer and neurological diseases, and emerging therapeutic strategies that exploit TE derepression, such as immunotherapies that target TE-derived tumour-specific antigens.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"62 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515441","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":"Good neighbours transfer nucleotides","authors":"Lisa Heinke","doi":"10.1038/s41580-025-00872-x","DOIUrl":"https://doi.org/10.1038/s41580-025-00872-x","url":null,"abstract":"Adequate levels of nucleotides are essential to ensure genetic stability of proliferating cells. A study finds gap-junction-mediated transport of nucleotides in specific tissues of Drosophila.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370467","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}
Tito Calì,Emmanuelle M Bayer,Emily R Eden,György Hajnóczky,Benoit Kornmann,Laura Lackner,Jen Liou,Karin Reinisch,Hyun-Woo Rhee,Rosario Rizzuto,Luca Scorrano,Marisa Brini
{"title":"Key challenges and recommendations for defining organelle membrane contact sites.","authors":"Tito Calì,Emmanuelle M Bayer,Emily R Eden,György Hajnóczky,Benoit Kornmann,Laura Lackner,Jen Liou,Karin Reinisch,Hyun-Woo Rhee,Rosario Rizzuto,Luca Scorrano,Marisa Brini","doi":"10.1038/s41580-025-00864-x","DOIUrl":"https://doi.org/10.1038/s41580-025-00864-x","url":null,"abstract":"Intracellular membrane contact sites (MCSs) between organelles have crucial roles in cellular signalling and homeostasis. These sites, which are often disrupted in pathological conditions, enable the exchange of ions, lipids and metabolites between membrane-bound compartments, helping cells adapt to varying physiological conditions. Specific tether proteins and complexes stabilize these interactions and mediate responses to different intracellular or extracellular stimuli. The study of MCSs has progressed in recent years, owing to the development of new methods such as genetically encoded reporter constructs, advanced imaging techniques, including super-resolution microscopy and electron tomography, and proteomic approaches based on mass spectrometry. These tools have enabled unprecedented visualization and quantification of organelle interactions, as well as identification of the molecular players involved. This Expert Recommendation aims to define and map the 'organelle contactome', describing key proteins involved in contact site formation and the roles of MCSs in cellular function. We also explore contact site dynamics and detail advantages and disadvantages of the methodologies for studying them. Importantly, we consolidate open questions in contact site research and discuss challenges and limitations of the current experimental approaches.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"23 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370324","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}
Vincent Jung, Cédric Vincent-Cuaz, Charlotte Tumescheit, Lisa Fournier, Marousa Darsinou, Zhi Ming Xu, Ali Saadat, Yiran Wang, Petros Tsantoulis, Olivier Michielin, Jacques Fellay, Rickie Patani, Andres Ramos, Pascal Frossard, Janna Hastings, Antonella Riccio, Lonneke van der Plas, Raphaëlle Luisier
{"title":"Decoding the interactions and functions of non-coding RNA with artificial intelligence","authors":"Vincent Jung, Cédric Vincent-Cuaz, Charlotte Tumescheit, Lisa Fournier, Marousa Darsinou, Zhi Ming Xu, Ali Saadat, Yiran Wang, Petros Tsantoulis, Olivier Michielin, Jacques Fellay, Rickie Patani, Andres Ramos, Pascal Frossard, Janna Hastings, Antonella Riccio, Lonneke van der Plas, Raphaëlle Luisier","doi":"10.1038/s41580-025-00857-w","DOIUrl":"https://doi.org/10.1038/s41580-025-00857-w","url":null,"abstract":"<p>In addition to encoding proteins, mRNAs have context-specific regulatory roles that contribute to many cellular processes. However, uncovering new mRNA functions is constrained by limitations of traditional biochemical and computational methods. In this Roadmap, we highlight how artificial intelligence can transform our understanding of RNA biology by fostering collaborations between RNA biologists and computational scientists to drive innovation in this fundamental field of research. We discuss how non-coding regions of the mRNA, including introns and 5′ and 3′ untranslated regions, regulate the metabolism and interactomes of mRNA, and the current challenges in characterizing these regions. We further discuss large language models, which can be used to learn biologically meaningful RNA sequence representations. We also provide a detailed roadmap for integrating large language models with graph neural networks to harness publicly available sequencing and knowledge data. Adopting this roadmap will allow us to predict RNA interactions with diverse molecules and the modelling of context-specific mRNA interactomes.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"97 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319501","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":"How machine learning can help us understand what we have grown in the dish","authors":"Roser Vento-Tormo","doi":"10.1038/s41580-025-00868-7","DOIUrl":"https://doi.org/10.1038/s41580-025-00868-7","url":null,"abstract":"A machine learning model was trained to quantify how closely neurons differentiated in a dish from stem cells resemble those found in the brain.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"17 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252302","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":"Collective migration modes in development, tissue repair and cancer","authors":"Kevin J. Cheung, Sally Horne-Badovinac","doi":"10.1038/s41580-025-00858-9","DOIUrl":"https://doi.org/10.1038/s41580-025-00858-9","url":null,"abstract":"<p>Migrating cells have key functions in shaping tissues during development, repairing tissues after development and supporting cancer invasion and metastasis. In all these contexts, cells often maintain contact with their neighbours and move as a group, in a process termed collective migration. In this Review, we describe the elegant mechanisms used by collectively migrating cells in vivo to coordinate their movements and obtain directional information. We start by highlighting the diverse physiological roles that migrating collectives have within the body and then focus on dominant paradigms for the organization of migrating collectives including the roles of leader and follower cells, local cell–cell adhesion and signalling, and external guidance cues. By comparing collective migrations occurring during development and cancer, we bring into focus shared principles for collective cell movement and distinct strategies used by cancer cells for their own dispersal. Throughout, we pay particular attention to how migrating collectives display emergent properties not exhibited by individually migrating cells and how these properties provide the robustness needed for efficient cell movement.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"19 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228678","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":"Nucleosomes as blueprints of genome architecture","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-025-00866-9","DOIUrl":"10.1038/s41580-025-00866-9","url":null,"abstract":"Nucleosomes — the basic unit of chromatin architecture — have intrinsic biophysical features of large-scale genome organization.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 7","pages":"500-500"},"PeriodicalIF":81.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211403","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}