Nature Cell Biology最新文献

{"title":"AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress","authors":"Xuewei Zhai, Ronghui Yang, Qiaoyun Chu, Zihao Guo, Pengjiao Hou, Xuexue Li, Changsen Bai, Ziwen Lu, Luxin Qiao, Yanxia Fu, Jing Niu, Binghui Li","doi":"10.1038/s41556-024-01549-x","DOIUrl":"10.1038/s41556-024-01549-x","url":null,"abstract":"Glucose metabolism has been studied extensively, but the role of glucose-derived excretory glycerol remains unclear. Here we show that hypoxia induces NADH accumulation to promote glycerol excretion and this pathway consumes NADH continuously, thus attenuating its accumulation and reductive stress. Aldolase B accounts for glycerol biosynthesis by forming a complex with glycerol 3-phosphate dehydrogenases GPD1 and GPD1L. Blocking GPD1, GPD1L or glycerol 3-phosphate phosphatase exacerbates reductive stress and suppresses cell proliferation under hypoxia and tumour growth in vivo. Overexpression of these enzymes increases glycerol excretion but still reduces cell viability under hypoxia and tumour proliferation due to energy stress. AMPK inactivates aldolase B to mitigate glycerol synthesis that dissipates ATP, alleviating NADH accumulation-induced energy crisis. Therefore, glycerol biosynthesis/excretion regulates the trade-off between reductive stress and energy stress. Moreover, this mode of regulation seems to be prevalent in reductive stress-driven transformations, enhancing our understanding of the metabolic complexity and guiding tumour treatment. Zhai, Yang et al. report a central role for AMPK in regulating aldolase B-mediated glycerol synthesis and excretion under hypoxia as a mechanism to balance the trade-off between reductive and energy stress during tumour growth.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":"141-153"},"PeriodicalIF":17.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911644","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":"TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling","authors":"Wei-Ting Lu, Lykourgos-Panagiotis Zalmas, Chris Bailey, James R. M. Black, Carlos Martinez-Ruiz, Oriol Pich, Francisco Gimeno-Valiente, Ieva Usaite, Alastair Magness, Kerstin Thol, Thomas A. Webber, Ming Jiang, Rebecca E. Saunders, Yun-Hsin Liu, Dhruva Biswas, Esther O. Ige, Birgit Aerne, Eva Grönroos, Subramanian Venkatesan, Georgia Stavrou, Takahiro Karasaki, Maise Al Bakir, Matthew Renshaw, Hang Xu, Deborah Schneider-Luftman, Natasha Sharma, Laura Tovini, TRACERx Consortium, Mariam Jamal-Hanjani, Sarah E. McClelland, Kevin Litchfield, Nicolai J. Birkbak, Michael Howell, Nicolas Tapon, Kasper Fugger, Nicholas McGranahan, Jiri Bartek, Nnennaya Kanu, Charles Swanton","doi":"10.1038/s41556-024-01558-w","DOIUrl":"10.1038/s41556-024-01558-w","url":null,"abstract":"Chromosomal instability (CIN) is common in solid tumours and fuels evolutionary adaptation and poor prognosis by increasing intratumour heterogeneity. Systematic characterization of driver events in the TRACERx non-small-cell lung cancer (NSCLC) cohort identified that genetic alterations in six genes, including FAT1, result in homologous recombination (HR) repair deficiencies and CIN. Using orthogonal genetic and experimental approaches, we demonstrate that FAT1 alterations are positively selected before genome doubling and associated with HR deficiency. FAT1 ablation causes persistent replication stress, an elevated mitotic failure rate, nuclear deformation and elevated structural CIN, including chromosome translocations and radial chromosomes. FAT1 loss contributes to whole-genome doubling (a form of numerical CIN) through the dysregulation of YAP1. Co-depletion of YAP1 partially rescues numerical CIN caused by FAT1 loss but does not relieve HR deficiencies, nor structural CIN. Importantly, overexpression of constitutively active YAP15SA is sufficient to induce numerical CIN. Taken together, we show that FAT1 loss in NSCLC attenuates HR and exacerbates CIN through two distinct downstream mechanisms, leading to increased tumour heterogeneity. Lu et al. perform systematic functional analyses using data from the TRACERx cohort of patients with non-small-cell lung cancer and delineate how FAT1 regulates homologous recombination repair, chromosomal instability and whole-genome doubling with distinct mechanisms.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":"154-168"},"PeriodicalIF":17.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01558-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904746","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}

{"title":"Bridging art and science","authors":"Sabrya Carim","doi":"10.1038/s41556-024-01587-5","DOIUrl":"10.1038/s41556-024-01587-5","url":null,"abstract":"Ahna Skop is a geneticist and artist at the University of Wisconsin–Madison, USA. Ahna’s lab studies the assembly and function of mammalian midbody and midbody remnant, which are assembled at the end of mitosis. Ahna also leans into her passion for scientific art to engage the public. We were fascinated to hear Ahna’s thoughts on open questions and challenges in the field and to learn about her passion of marrying science and art.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":"2-3"},"PeriodicalIF":17.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858397","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":"Worrying through the ECM","authors":"Daryl J. V. David","doi":"10.1038/s41556-024-01579-5","DOIUrl":"10.1038/s41556-024-01579-5","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2013-2013"},"PeriodicalIF":17.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798571","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":"Cu in cancer metabolism","authors":"Zhe Wang","doi":"10.1038/s41556-024-01578-6","DOIUrl":"10.1038/s41556-024-01578-6","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2013-2013"},"PeriodicalIF":17.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798553","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":"Regulating chromatin assembly","authors":"Sabrya Carim","doi":"10.1038/s41556-024-01581-x","DOIUrl":"10.1038/s41556-024-01581-x","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2013-2013"},"PeriodicalIF":17.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798588","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":"Making stronger T cells","authors":"Stylianos Lefkopoulos","doi":"10.1038/s41556-024-01577-7","DOIUrl":"10.1038/s41556-024-01577-7","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2013-2013"},"PeriodicalIF":17.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798600","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":"Women in Autophagy: an initiative to promote gender parity in science","authors":"Mericka McCabe, Patricia Boya, Ruey-Hwa Chen, Charleen T. Chu, Maria Isabel Colombo, Laura Delgui, Eeva-Liisa Eskelinen, Maho Hamasaki, Malene Hansen, Congcong He, Marja Jäättelä, Adi Kimchi, Claudine Kraft, Mondira Kundu, Alicia Melendez, Sophie Pattingre, Tassula Proikas-Cezanne, Salwa Sebti, Anna Katharina Simon, Anne Simonsen, Sharon A. Tooze, Maria Ines Vaccaro, Xiaochen Wang, Eileen White, Yan Zhao, Ana Maria Cuervo","doi":"10.1038/s41556-024-01566-w","DOIUrl":"10.1038/s41556-024-01566-w","url":null,"abstract":"Scientific questions are universal but the scientific workforce remains skewed, with women and gender minorities still underrepresented. Initiatives such as the Women in Autophagy network promote the careers of these underrepresented groups with a range of free, year-round scientific, mentoring and networking activities for all scientists.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2009-2012"},"PeriodicalIF":17.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758454","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":"Author Correction: Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum","authors":"Yang Yang, Luis A. Valencia, Chih-Hao Lu, Melissa L. Nakamoto, Ching-Ting Tsai, Chun Liu, Huaxiao Yang, Wei Zhang, Zeinab Jahed, Wan-Ru Lee, Francesca Santoro, Jen Liou, Joseph C. Wu, Bianxiao Cui","doi":"10.1038/s41556-024-01585-7","DOIUrl":"https://doi.org/10.1038/s41556-024-01585-7","url":null,"abstract":"<p>Correction to: <i>Nature Cell Biology</i> https://doi.org/10.1038/s41556-024-01511-x, published online 17 September 2024.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"12 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758371","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":"The enhancer module of Integrator controls cell identity and early neural fate commitment","authors":"Yingjie Zhang,&nbsp;Connor M. Hill,&nbsp;Kelsey A. Leach,&nbsp;Luca Grillini,&nbsp;Sandra Deliard,&nbsp;Sarah R. Offley,&nbsp;Martina Gatto,&nbsp;Francis Picone,&nbsp;Avery Zucco,&nbsp;Alessandro Gardini","doi":"10.1038/s41556-024-01556-y","DOIUrl":"10.1038/s41556-024-01556-y","url":null,"abstract":"Lineage-specific transcription factors operate as master orchestrators of developmental processes by activating select cis-regulatory enhancers and proximal promoters. Direct DNA binding of transcription factors ultimately drives context-specific recruitment of the basal transcriptional machinery that comprises RNA polymerase II (RNAPII) and a host of polymerase-associated multiprotein complexes, including the metazoan-specific Integrator complex. Integrator is primarily known to modulate RNAPII processivity and to surveil RNA integrity across coding genes. Here we describe an enhancer module of Integrator that directs cell fate specification by promoting epigenetic changes and transcription factor binding at neural enhancers. Depletion of Integrator’s INTS10 subunit upends neural traits and derails cells towards mesenchymal identity. Commissioning of neural enhancers relies on Integrator’s enhancer module, which stabilizes SOX2 binding at chromatin upon exit from pluripotency. We propose that Integrator is a functional bridge between enhancers and promoters and a main driver of early development, providing new insight into a growing family of neurodevelopmental syndromes. Zhang et al. report that INST10, part of the Integrator enhancer module, promotes epigenetic changes and transcription factor binding at enhancers that drive neural cell fate commitment by stabilizing SOX2 binding at chromatin upon pluripotency exit.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":"103-117"},"PeriodicalIF":17.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142713099","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}