Nature Cell Biology最新文献_第10页

TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA TFAM 是一种自噬受体，它通过与细胞质线粒体 DNA 结合来限制炎症的发生

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-23 DOI: 10.1038/s41556-024-01419-6

Hao Liu, Cien Zhen, Jianming Xie, Zhenhuan Luo, Lin Zeng, Guojun Zhao, Shaohua Lu, Haixia Zhuang, Hualin Fan, Xia Li, Zhaojie Liu, Shiyin Lin, Huilin Jiang, Yuqian Chen, Jiahao Cheng, Zhiyu Cao, Keyu Dai, Jinhua Shi, Zhaohua Wang, Yongquan Hu, Tian Meng, Chuchu Zhou, Zhiyuan Han, Huansen Huang, Qinghua Zhou, Pengcheng He, Du Feng

{"title":"TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA","authors":"Hao Liu, Cien Zhen, Jianming Xie, Zhenhuan Luo, Lin Zeng, Guojun Zhao, Shaohua Lu, Haixia Zhuang, Hualin Fan, Xia Li, Zhaojie Liu, Shiyin Lin, Huilin Jiang, Yuqian Chen, Jiahao Cheng, Zhiyu Cao, Keyu Dai, Jinhua Shi, Zhaohua Wang, Yongquan Hu, Tian Meng, Chuchu Zhou, Zhiyuan Han, Huansen Huang, Qinghua Zhou, Pengcheng He, Du Feng","doi":"10.1038/s41556-024-01419-6","DOIUrl":"10.1038/s41556-024-01419-6","url":null,"abstract":"When cells are stressed, DNA from energy-producing mitochondria can leak out and drive inflammatory immune responses if not cleared. Cells employ a quality control system called autophagy to specifically degrade damaged components. We discovered that mitochondrial transcription factor A (TFAM)—a protein that binds mitochondrial DNA (mtDNA)—helps to eliminate leaked mtDNA by interacting with the autophagy protein LC3 through an autolysosomal pathway (we term this nucleoid-phagy). TFAM contains a molecular zip code called the LC3 interacting region (LIR) motif that enables this binding. Although mutating TFAM’s LIR motif did not affect its normal mitochondrial functions, more mtDNA accumulated in the cell cytoplasm, activating inflammatory signalling pathways. Thus, TFAM mediates autophagic removal of leaked mtDNA to restrict inflammation. Identifying this mechanism advances understanding of how cells exploit autophagy machinery to selectively target and degrade inflammatory mtDNA. These findings could inform research on diseases involving mitochondrial damage and inflammation. Liu, Zhen, Xie, Luo, Zeng, Zhao et al. show that the major nucleoid protein TFAM interacts with cytoplasmic LC3B during oxidative or inflammatory stress to attenuate mitochondrial DNA-induced inflammation via the cGAS–STING pathway.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085557","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

Author Correction: mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype 作者更正：mTOR 调节 MAPKAPK2 翻译以控制衰老相关的分泌表型

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-22 DOI: 10.1038/s41556-024-01443-6

Nicolás Herranz, Suchira Gallage, Massimiliano Mellone, Torsten Wuestefeld, Sabrina Klotz, Christopher J. Hanley, Selina Raguz, Juan Carlos Acosta, Andrew J. Innes, Ana Banito, Athena Georgilis, Alex Montoya, Katharina Wolter, Gopuraja Dharmalingam, Peter Faull, Thomas Carroll, Juan Pedro Martínez-Barbera, Pedro Cutillas, Florian Reisinger, Mathias Heikenwalder, Richard A. Miller, Dominic Withers, Lars Zender, Gareth J. Thomas, Jesús Gil

引用次数: 0

Mitochondrial heterogeneity and adaptations to cellular needs 线粒体的异质性和对细胞需求的适应性

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-16 DOI: 10.1038/s41556-024-01410-1

Melia Granath-Panelo, Shingo Kajimura

引用次数: 0

Phase separation-competent FBL promotes early pre-rRNA processing and translation in acute myeloid leukaemia 相分离能力强的 FBL 可促进急性髓性白血病的早期前 RNA 处理和翻译

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-14 DOI: 10.1038/s41556-024-01420-z

Lin Yang, Zhaoru Zhang, Penglei Jiang, Delin Kong, Zebin Yu, Danrong Shi, Yingli Han, Ertuo Chen, Weiyan Zheng, Jie Sun, Yanmin Zhao, Yi Luo, Jimin Shi, Hangping Yao, He Huang, Pengxu Qian

{"title":"Phase separation-competent FBL promotes early pre-rRNA processing and translation in acute myeloid leukaemia","authors":"Lin Yang, Zhaoru Zhang, Penglei Jiang, Delin Kong, Zebin Yu, Danrong Shi, Yingli Han, Ertuo Chen, Weiyan Zheng, Jie Sun, Yanmin Zhao, Yi Luo, Jimin Shi, Hangping Yao, He Huang, Pengxu Qian","doi":"10.1038/s41556-024-01420-z","DOIUrl":"10.1038/s41556-024-01420-z","url":null,"abstract":"RNA-binding proteins (RBPs) are pivotal in acute myeloid leukaemia (AML), a lethal disease. Although specific phase separation-competent RBPs are recognized in AML, the effect of their condensate formation on AML leukaemogenesis, and the therapeutic potential of inhibition of phase separation are underexplored. In our in vivo CRISPR RBP screen, fibrillarin (FBL) emerges as a crucial nucleolar protein that regulates AML cell survival, primarily through its phase separation domains rather than methyltransferase or acetylation domains. These phase separation domains, with specific features, coordinately drive nucleoli formation and early processing of pre-rRNA (including efflux, cleavage and methylation), eventually enhancing the translation of oncogenes such as MYC. Targeting the phase separation capability of FBL with CGX-635 leads to elimination of AML cells, suggesting an additional mechanism of action for CGX-635 that complements its established therapeutic effects. We highlight the potential of PS modulation of critical proteins as a possible therapeutic strategy for AML. Yang et al. report that the nucleolar protein fibrillarin (FBL) affects acute myeloid leukaemia (AML) cell function through biomolecular condensation-dependent regulation of early pre-rRNA processing and translation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140919481","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

Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington’s disease 多聚谷氨酰胺介导的核糖毒性会破坏亨廷顿氏病的蛋白稳态和应激反应

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-13 DOI: 10.1038/s41556-024-01414-x

Ranen Aviner, Ting-Ting Lee, Vincent B. Masto, Kathy H. Li, Raul Andino, Judith Frydman

{"title":"Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington’s disease","authors":"Ranen Aviner, Ting-Ting Lee, Vincent B. Masto, Kathy H. Li, Raul Andino, Judith Frydman","doi":"10.1038/s41556-024-01414-x","DOIUrl":"10.1038/s41556-024-01414-x","url":null,"abstract":"Huntington’s disease (HD) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat in the Huntingtin (HTT) gene, encoding a homopolymeric polyglutamine (polyQ) tract. Although mutant HTT (mHTT) protein is known to aggregate, the links between aggregation and neurotoxicity remain unclear. Here we show that both translation and aggregation of wild-type HTT and mHTT are regulated by a stress-responsive upstream open reading frame and that polyQ expansions cause abortive translation termination and release of truncated, aggregation-prone mHTT fragments. Notably, we find that mHTT depletes translation elongation factor eIF5A in brains of symptomatic HD mice and cultured HD cells, leading to pervasive ribosome pausing and collisions. Loss of eIF5A disrupts homeostatic controls and impairs recovery from acute stress. Importantly, drugs that inhibit translation initiation reduce premature termination and mitigate this escalating cascade of ribotoxic stress and dysfunction in HD. Aviner et al. show that translation and aggregation of Huntingtin (HTT) are regulated by a stress-responsive upstream open reading frame. Mutant HTT depletes translation elongation factor eIF5A, leading to ribosome pausing and collisions.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915078","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

It takes two to expand the cortex 扩大皮质需要两个人

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-07 DOI: 10.1038/s41556-024-01416-9

Yechiel Elkabetz

引用次数: 0

Cell-intrinsic and microenvironmental determinants of metastatic colonization 转移性定植的细胞内在因素和微环境决定因素

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-07 DOI: 10.1038/s41556-024-01409-8

Arthur W. Lambert, Yun Zhang, Robert A. Weinberg

{"title":"Cell-intrinsic and microenvironmental determinants of metastatic colonization","authors":"Arthur W. Lambert, Yun Zhang, Robert A. Weinberg","doi":"10.1038/s41556-024-01409-8","DOIUrl":"10.1038/s41556-024-01409-8","url":null,"abstract":"Cancer metastasis is a biologically complex process that remains a major challenge in the oncology clinic, accounting for nearly all of the mortality associated with malignant neoplasms. To establish metastatic growths, carcinoma cells must disseminate from the primary tumour, survive in unfamiliar tissue microenvironments, re-activate programs of proliferation, and escape innate and adaptive immunosurveillance. The entire process is extremely inefficient and can occur over protracted timescales, yielding only a vanishingly small number of carcinoma cells that are able to complete all of the required steps. Here we review both the cancer-cell-intrinsic mechanisms and microenvironmental interactions that enable metastatic colonization. In particular, we highlight recent work on the behaviour of already-disseminated tumour cells, since meaningful progress in treating metastatic disease will clearly require a better understanding of the cells that spawn metastases, which generally have disseminated by the time of initial diagnosis. Metastatic colonization involves cancer-cell-intrinsic mechanisms and microenvironmental interactions, and a better understanding of the factors that influence the final, post-extravasation phases is crucial for therapeutically targeting metatstasis.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845067","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

Cerebral organoids display dynamic clonal growth and tunable tissue replenishment 脑器官组织显示出动态克隆生长和可调的组织补充能力

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-07 DOI: 10.1038/s41556-024-01412-z

Dominik Lindenhofer, Simon Haendeler, Christopher Esk, Jamie B. Littleboy, Clarisse Brunet Avalos, Julia Naas, Florian G. Pflug, Eline G. P. van de Ven, Daniel Reumann, Alexandre D. Baffet, Arndt von Haeseler, Jürgen A. Knoblich

{"title":"Cerebral organoids display dynamic clonal growth and tunable tissue replenishment","authors":"Dominik Lindenhofer, Simon Haendeler, Christopher Esk, Jamie B. Littleboy, Clarisse Brunet Avalos, Julia Naas, Florian G. Pflug, Eline G. P. van de Ven, Daniel Reumann, Alexandre D. Baffet, Arndt von Haeseler, Jürgen A. Knoblich","doi":"10.1038/s41556-024-01412-z","DOIUrl":"10.1038/s41556-024-01412-z","url":null,"abstract":"During brain development, neural progenitors expand through symmetric divisions before giving rise to differentiating cell types via asymmetric divisions. Transition between those modes varies among individual neural stem cells, resulting in clones of different sizes. Imaging-based lineage tracing allows for lineage analysis at high cellular resolution but systematic approaches to analyse clonal behaviour of entire tissues are currently lacking. Here we implement whole-tissue lineage tracing by genomic DNA barcoding in 3D human cerebral organoids, to show that individual stem cell clones produce progeny on a vastly variable scale. By using stochastic modelling we find that variable lineage sizes arise because a subpopulation of lineages retains symmetrically dividing cells. We show that lineage sizes can adjust to tissue demands after growth perturbation via chemical ablation or genetic restriction of a subset of cells in chimeric organoids. Our data suggest that adaptive plasticity of stem cell populations ensures robustness of development in human brain organoids. Lindenhofer, Haendeler, Esk, Littleboy et al. perform whole-tissue lineage tracing in human cerebral organoids to reveal that a subpopulation of symmetrically dividing cells can adjust its lineage size depending on tissue demands.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01412-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845328","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

Mammalian IRE1α dynamically and functionally coalesces with stress granules 哺乳动物 IRE1α 在动态和功能上与应激颗粒凝聚在一起

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-07 DOI: 10.1038/s41556-024-01418-7

Songzi Liu, Xiaoge Zhang, Xin Yao, Guan Wang, Shijia Huang, Peng Chen, Mingliang Tang, Jie Cai, Zhuyin Wu, Yiliang Zhang, Rongzhi Xu, Kai Liu, Kangmin He, Yan Wang, Lei Jiang, Qiong A. Wang, Liangyou Rui, Jianmiao Liu, Yong Liu

{"title":"Mammalian IRE1α dynamically and functionally coalesces with stress granules","authors":"Songzi Liu, Xiaoge Zhang, Xin Yao, Guan Wang, Shijia Huang, Peng Chen, Mingliang Tang, Jie Cai, Zhuyin Wu, Yiliang Zhang, Rongzhi Xu, Kai Liu, Kangmin He, Yan Wang, Lei Jiang, Qiong A. Wang, Liangyou Rui, Jianmiao Liu, Yong Liu","doi":"10.1038/s41556-024-01418-7","DOIUrl":"10.1038/s41556-024-01418-7","url":null,"abstract":"Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α–SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α–XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α–SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity. Liu, Zhang, Yao et al. report that IRE1 α clustering, known to be part of the unfolded protein response, is membrane-bound phase separation and that IRE1 can coalesce with the phase-separated stress granules.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845087","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

ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification ETV4是一种将细胞拥挤动力学与血统规格化联系起来的机械换能器

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-05-03 DOI: 10.1038/s41556-024-01415-w

Seungbok Yang, Mahdi Golkaram, Seyoun Oh, Yujeong Oh, Yoonjae Cho, Jeehyun Yoe, Sungeun Ju, Matthew A. Lalli, Seung-Yeol Park, Yoontae Lee, Jiwon Jang

{"title":"ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification","authors":"Seungbok Yang, Mahdi Golkaram, Seyoun Oh, Yujeong Oh, Yoonjae Cho, Jeehyun Yoe, Sungeun Ju, Matthew A. Lalli, Seung-Yeol Park, Yoontae Lee, Jiwon Jang","doi":"10.1038/s41556-024-01415-w","DOIUrl":"10.1038/s41556-024-01415-w","url":null,"abstract":"Dynamic changes in mechanical microenvironments, such as cell crowding, regulate lineage fates as well as cell proliferation. Although regulatory mechanisms for contact inhibition of proliferation have been extensively studied, it remains unclear how cell crowding induces lineage specification. Here we found that a well-known oncogene, ETS variant transcription factor 4 (ETV4), serves as a molecular transducer that links mechanical microenvironments and gene expression. In a growing epithelium of human embryonic stem cells, cell crowding dynamics is translated into ETV4 expression, serving as a pre-pattern for future lineage fates. A switch-like ETV4 inactivation by cell crowding derepresses the potential for neuroectoderm differentiation in human embryonic stem cell epithelia. Mechanistically, cell crowding inactivates the integrin–actomyosin pathway and blocks the endocytosis of fibroblast growth factor receptors (FGFRs). The disrupted FGFR endocytosis induces a marked decrease in ETV4 protein stability through ERK inactivation. Mathematical modelling demonstrates that the dynamics of cell density in a growing human embryonic stem cell epithelium precisely determines the spatiotemporal ETV4 expression pattern and, consequently, the timing and geometry of lineage development. Our findings suggest that cell crowding dynamics in a stem cell epithelium drives spatiotemporal lineage specification using ETV4 as a key mechanical transducer. Yang, Golkaram et al. reported that in human embryonic stem cells, cellular crowding leads to the blockade of FGFR1 endocytosis, resulting in a decrease in ETV4 expression. This, in turn, derepresses the neuroectoderm fate.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01415-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821114","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