Pub Date : 2025-07-31DOI: 10.1038/s41580-025-00880-x
Emma Pasquier, Chems Amari
In this Tools of the Trade article, Pasquier and Amari (Gueroui lab) describe the development of ControLD, which allows the intracellular sequestration of organelles through condensate formation, enabling the control of inter-organelle communication.
{"title":"Condensate-mediated intracellular organelle sequestration","authors":"Emma Pasquier, Chems Amari","doi":"10.1038/s41580-025-00880-x","DOIUrl":"10.1038/s41580-025-00880-x","url":null,"abstract":"In this Tools of the Trade article, Pasquier and Amari (Gueroui lab) describe the development of ControLD, which allows the intracellular sequestration of organelles through condensate formation, enabling the control of inter-organelle communication.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 10","pages":"734-734"},"PeriodicalIF":90.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756547","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}
Pub Date : 2025-07-18DOI: 10.1038/s41580-025-00871-y
Yu Yu, Han Wang, Chenjiang You, Xuemei Chen
Since their discovery in 2002, much has been learnt about plant microRNAs (miRNAs), including the genes that encode them and the target genes that they regulate; the microprocessor complex that produces the miRNAs and the effector ARGONAUTE (AGO) proteins with which miRNAs associate; the mechanisms of target-RNA recognition by miRNAs and miRNA modes of action; miRNA subcellular localization; and miRNA mobility between cells and within plants. In this Review, we discuss new mechanistic insights into miRNA maturation and AGO loading, the subcellular locations of miRNA processing and activity and partitioning of miRNAs between the nucleus and cytoplasm, which in turn affects their intercellular mobility. We also discuss intriguing connections between miRNAs and the translation process and present hypotheses to be tested by future studies. This Review discusses new mechanistic insights into plant microRNA maturation, intercellular and tissue mobility and the intriguing interplay between microRNAs and the translation process.
{"title":"Plant microRNA maturation and function","authors":"Yu Yu, Han Wang, Chenjiang You, Xuemei Chen","doi":"10.1038/s41580-025-00871-y","DOIUrl":"10.1038/s41580-025-00871-y","url":null,"abstract":"Since their discovery in 2002, much has been learnt about plant microRNAs (miRNAs), including the genes that encode them and the target genes that they regulate; the microprocessor complex that produces the miRNAs and the effector ARGONAUTE (AGO) proteins with which miRNAs associate; the mechanisms of target-RNA recognition by miRNAs and miRNA modes of action; miRNA subcellular localization; and miRNA mobility between cells and within plants. In this Review, we discuss new mechanistic insights into miRNA maturation and AGO loading, the subcellular locations of miRNA processing and activity and partitioning of miRNAs between the nucleus and cytoplasm, which in turn affects their intercellular mobility. We also discuss intriguing connections between miRNAs and the translation process and present hypotheses to be tested by future studies. This Review discusses new mechanistic insights into plant microRNA maturation, intercellular and tissue mobility and the intriguing interplay between microRNAs and the translation process.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 1","pages":"55-70"},"PeriodicalIF":90.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652568","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}
Pub Date : 2025-07-16DOI: 10.1038/s41580-025-00877-6
Matthew P. Johnson
{"title":"Author Correction: Structure, regulation and assembly of the photosynthetic electron transport chain","authors":"Matthew P. Johnson","doi":"10.1038/s41580-025-00877-6","DOIUrl":"10.1038/s41580-025-00877-6","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 9","pages":"725-725"},"PeriodicalIF":90.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41580-025-00877-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640362","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}
Pub Date : 2025-07-14DOI: 10.1038/s41580-025-00870-z
Zhiqian Zhang, Elijah L. Mena, Richard T. Timms, Itay Koren, Stephen J. Elledge
Degrons are pivotal components of the ubiquitin–proteasome system, serving as the recognition determinants through which E3 ubiquitin ligases identify their substrates. Degrons have central roles in both protein quality control and intracellular signalling pathways, and mutations that dysregulate degron activity are associated with a wide range of diseases, including cancer, immunological disorders and neurodegeneration. The number of well-defined degrons remains sparse relative to the ~600 E3 ubiquitin ligases encoded in the human genome. Recent advances in high-throughput degron discovery technologies have accelerated progress in this area, expanding the number of N- and C-terminal degrons, internal degrons and ubiquitin-independent degrons defined experimentally at high resolution. In this Review, we discuss the latest insights into the molecular mechanisms through which degrons act, their functional importance and their relevance in human disease, and consider how bifunctional molecules harness degrons to enable targeted protein degradation for therapeutic benefit. Degrons allow E3 ubiquitin ligases to identify their substrates, and thus have a central role in protein degradation by the ubiquitin–proteasome system. This Review discusses the latest insights into the mechanisms underlying degron function, the relevance of degrons in disease and how degrons can be harnessed for therapeutic protein degradation.
{"title":"Degrons: defining the rules of protein degradation","authors":"Zhiqian Zhang, Elijah L. Mena, Richard T. Timms, Itay Koren, Stephen J. Elledge","doi":"10.1038/s41580-025-00870-z","DOIUrl":"10.1038/s41580-025-00870-z","url":null,"abstract":"Degrons are pivotal components of the ubiquitin–proteasome system, serving as the recognition determinants through which E3 ubiquitin ligases identify their substrates. Degrons have central roles in both protein quality control and intracellular signalling pathways, and mutations that dysregulate degron activity are associated with a wide range of diseases, including cancer, immunological disorders and neurodegeneration. The number of well-defined degrons remains sparse relative to the ~600 E3 ubiquitin ligases encoded in the human genome. Recent advances in high-throughput degron discovery technologies have accelerated progress in this area, expanding the number of N- and C-terminal degrons, internal degrons and ubiquitin-independent degrons defined experimentally at high resolution. In this Review, we discuss the latest insights into the molecular mechanisms through which degrons act, their functional importance and their relevance in human disease, and consider how bifunctional molecules harness degrons to enable targeted protein degradation for therapeutic benefit. Degrons allow E3 ubiquitin ligases to identify their substrates, and thus have a central role in protein degradation by the ubiquitin–proteasome system. This Review discusses the latest insights into the mechanisms underlying degron function, the relevance of degrons in disease and how degrons can be harnessed for therapeutic protein degradation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 11","pages":"868-883"},"PeriodicalIF":90.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622479","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}
Pub Date : 2025-07-08DOI: 10.1038/s41580-025-00874-9
Lisa Heinke
Kleptosomes are specialized organelles harbouring photosynthetically active chloroplasts that are taken up by so-called ‘solar-powered’ sea slugs.
窃液小体是一种特殊的细胞器，可以容纳光合作用活跃的叶绿体，这些叶绿体被所谓的“太阳能”海蛞蝓吸收。
{"title":"Kleptomaniac sea slugs steal their greens","authors":"Lisa Heinke","doi":"10.1038/s41580-025-00874-9","DOIUrl":"10.1038/s41580-025-00874-9","url":null,"abstract":"Kleptosomes are specialized organelles harbouring photosynthetically active chloroplasts that are taken up by so-called ‘solar-powered’ sea slugs.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 8","pages":"584-584"},"PeriodicalIF":81.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586324","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}
Pub Date : 2025-07-08DOI: 10.1038/s41580-025-00875-8
Kim Baumann
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.
{"title":"A redox–auxin connection in response to water deficit","authors":"Kim Baumann","doi":"10.1038/s41580-025-00875-8","DOIUrl":"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":"26 8","pages":"583-583"},"PeriodicalIF":81.3,"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}
Pub Date : 2025-07-03DOI: 10.1038/s41580-025-00865-w
Toshiya Endo, Nils Wiedemann
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. Mitochondrial proteins encoded in the nucleus are imported into mitochondria by specialized transport machineries located in the outer and inner mitochondrial membranes. This Review explores these diverse import pathways and highlights recent insights into the structural properties of the transport machinery.
{"title":"Molecular machineries and pathways of mitochondrial protein transport","authors":"Toshiya Endo, Nils Wiedemann","doi":"10.1038/s41580-025-00865-w","DOIUrl":"10.1038/s41580-025-00865-w","url":null,"abstract":"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. Mitochondrial proteins encoded in the nucleus are imported into mitochondria by specialized transport machineries located in the outer and inner mitochondrial membranes. This Review explores these diverse import pathways and highlights recent insights into the structural properties of the transport machinery.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 11","pages":"848-867"},"PeriodicalIF":90.2,"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}
Pub Date : 2025-07-02DOI: 10.1038/s41580-025-00869-6
Manuel Beltrán-Visiedo, Ruth Soler-Agesta, Kristopher A. Sarosiek, Douglas R. Green, Lorenzo Galluzzi
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. Mammalian caspases are a group of cysteine proteases historically categorized into an ‘inflammatory’ subgroup and an ‘apoptotic’ subgroup, although accumulating evidence indicates that this distinction is not as clearcut as initially thought. Here, we discuss the functions of inflammatory caspases and apoptotic caspases, while proposing that all caspases ultimately regulate inflammation, either directly or by controlling cell death.
{"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":"10.1038/s41580-025-00869-6","url":null,"abstract":"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. Mammalian caspases are a group of cysteine proteases historically categorized into an ‘inflammatory’ subgroup and an ‘apoptotic’ subgroup, although accumulating evidence indicates that this distinction is not as clearcut as initially thought. Here, we discuss the functions of inflammatory caspases and apoptotic caspases, while proposing that all caspases ultimately regulate inflammation, either directly or by controlling cell death.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 11","pages":"884-901"},"PeriodicalIF":90.2,"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}
Pub Date : 2025-06-30DOI: 10.1038/s41580-025-00867-8
İbrahim Avşar Ilık, Xu Yang, ZZ Zhao Zhang, Tuğçe Aktaş
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. Transposable elements (TEs) comprise nearly half of the human genome. This Review discusses transcriptional and post-transcriptional mechanisms that repress TE activity, how TEs escape this suppression and regulate endogenous genes in development and disease, and emerging therapeutic strategies that exploit TE derepression.
{"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":"10.1038/s41580-025-00867-8","url":null,"abstract":"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. Transposable elements (TEs) comprise nearly half of the human genome. This Review discusses transcriptional and post-transcriptional mechanisms that repress TE activity, how TEs escape this suppression and regulate endogenous genes in development and disease, and emerging therapeutic strategies that exploit TE derepression.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 10","pages":"759-775"},"PeriodicalIF":90.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41580-025-00867-8.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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