Nature Cell Biology最新文献_第3页

Precursor occupancy controls mitochondrial import channel via proteolysis 前体占用通过蛋白水解控制线粒体输入通道

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01575-9

引用次数: 0

Triacylglycerol mobilization underpins mitochondrial stress recovery 三酰基甘油动员支持线粒体应激恢复

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01586-6

Zakery N. Baker, Yunyun Zhu, Rachel M. Guerra, Andrew J. Smith, Aline Arra, Lia R. Serrano, Katherine A. Overmyer, Shankar Mukherji, Elizabeth A. Craig, Joshua J. Coon, David J. Pagliarini

{"title":"Triacylglycerol mobilization underpins mitochondrial stress recovery","authors":"Zakery N. Baker, Yunyun Zhu, Rachel M. Guerra, Andrew J. Smith, Aline Arra, Lia R. Serrano, Katherine A. Overmyer, Shankar Mukherji, Elizabeth A. Craig, Joshua J. Coon, David J. Pagliarini","doi":"10.1038/s41556-024-01586-6","DOIUrl":"https://doi.org/10.1038/s41556-024-01586-6","url":null,"abstract":"Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response. In particular, acyl chains from these stores were liberated by triacylglycerol lipases and used to fuel biosynthesis of the quintessential mitochondrial membrane lipid cardiolipin to support new mitochondrial biogenesis. We demonstrate that a comparable recovery pathway exists in mammalian cells, which fail to recover from doxycycline treatment when lacking the ATGL lipase. Collectively, our work reveals a key component of mitochondrial stress recovery and offers a rich resource for further exploration of the broad cellular responses to mitochondrial dysfunction.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936280","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

Misshapen chromosomes in check by mechanics 机械控制畸形染色体

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01573-x

Joana C. Macedo, Maria M. da Silva, Elsa Logarinho

引用次数: 0

Gallbladder-derived retinoic acid signalling drives reconstruction of the damaged intrahepatic biliary ducts 胆囊源性维甲酸信号驱动受损肝内胆管的重建

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01568-8

Jianbo He, Shuang Li, Zhuolin Yang, Jianlong Ma, Chuanfang Qian, Zhuofu Huang, Linke Li, Yun Yang, Jingying Chen, Yunfan Sun, Tianyu Zhao, Lingfei Luo

{"title":"Gallbladder-derived retinoic acid signalling drives reconstruction of the damaged intrahepatic biliary ducts","authors":"Jianbo He, Shuang Li, Zhuolin Yang, Jianlong Ma, Chuanfang Qian, Zhuofu Huang, Linke Li, Yun Yang, Jingying Chen, Yunfan Sun, Tianyu Zhao, Lingfei Luo","doi":"10.1038/s41556-024-01568-8","DOIUrl":"10.1038/s41556-024-01568-8","url":null,"abstract":"Severe damage to the intrahepatic biliary duct (IHBD) network occurs in multiple human advanced cholangiopathies, such as primary sclerosing cholangitis, biliary atresia and end-stage primary biliary cholangitis. Whether and how a severely damaged IHBD network could reconstruct has remained unclear. Here we show that, although the gallbladder is not directly connected to the IHBD, there is a common hepatic duct (CHD) in between, and severe damage to the IHBD network induces migration of gallbladder smooth muscle cells (SMCs) to coat the CHD in mouse and zebrafish models. These gallbladder-derived, CHD-coating SMCs produce retinoic acid to activate Sox9b in the CHD, which drives proliferation and ingrowth of CHD cells into the inner liver to reconstruct the IHBD network. This study reveals a hitherto unappreciated function of the gallbladder in the recovery of injured liver, and characterizes mechanisms involved in how the gallbladder and liver communicate through inter-organ cell migration to drive tissue regeneration. Carrying out cholecystectomy will thus cause previously unexpected impairments to liver health. Luo et al. show in zebrafish and mouse that, upon intrahepatic biliary duct damage, gallbladder smooth muscle cells migrate to the common hepatic duct, where they produce retinoic acid to promote regeneration of the intrahepatic biliary duct.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":"39-47"},"PeriodicalIF":17.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936061","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

H3K36 methylation regulates cell plasticity and regeneration in the intestinal epithelium H3K36甲基化调节肠上皮细胞的可塑性和再生

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01580-y

Alison R. S. Pashos, Anne R. Meyer, Cameron Bussey-Sutton, Erin S. O’Connor, Mariel Coradin, Marilyne Coulombe, Kent A. Riemondy, Sanjana Potlapelly, Brian D. Strahl, Gunnar C. Hansson, Peter J. Dempsey, Justin Brumbaugh

{"title":"H3K36 methylation regulates cell plasticity and regeneration in the intestinal epithelium","authors":"Alison R. S. Pashos, Anne R. Meyer, Cameron Bussey-Sutton, Erin S. O’Connor, Mariel Coradin, Marilyne Coulombe, Kent A. Riemondy, Sanjana Potlapelly, Brian D. Strahl, Gunnar C. Hansson, Peter J. Dempsey, Justin Brumbaugh","doi":"10.1038/s41556-024-01580-y","DOIUrl":"https://doi.org/10.1038/s41556-024-01580-y","url":null,"abstract":"Plasticity is needed during development and homeostasis to generate diverse cell types from stem and progenitor cells. Following differentiation, plasticity must be restricted in specialized cells to maintain tissue integrity and function. For this reason, specialized cell identity is stable under homeostatic conditions; however, cells in some tissues regain plasticity during injury-induced regeneration. While precise gene expression controls these processes, the regulatory mechanisms that restrict or promote cell plasticity are poorly understood. Here we use the mouse small intestine as a model system to study cell plasticity. We find that H3K36 methylation reinforces expression of cell-type-associated genes to maintain specialized cell identity in intestinal epithelial cells. Depleting H3K36 methylation disrupts lineage commitment and activates regenerative gene expression. Correspondingly, we observe rapid and reversible remodelling of H3K36 methylation following injury-induced regeneration. These data suggest a fundamental role for H3K36 methylation in reinforcing specialized lineages and regulating cell plasticity and regeneration.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"23 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936059","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

Mapping the developmental trajectory of human astrocytes reveals divergence in glioblastoma 绘制人类星形胶质细胞的发育轨迹揭示胶质母细胞瘤的分化

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01583-9

Caitlin Sojka, Hsiao-Lin V. Wang, Tarun N. Bhatia, Yangping Li, Pankaj Chopra, Anson Sing, Anna Voss, Alexia King, Feng Wang, Kevin Joseph, Vidhya M. Ravi, Jeffrey Olson, Kimberly Hoang, Edjah Nduom, Victor G. Corces, Bing Yao, Steven A. Sloan

{"title":"Mapping the developmental trajectory of human astrocytes reveals divergence in glioblastoma","authors":"Caitlin Sojka, Hsiao-Lin V. Wang, Tarun N. Bhatia, Yangping Li, Pankaj Chopra, Anson Sing, Anna Voss, Alexia King, Feng Wang, Kevin Joseph, Vidhya M. Ravi, Jeffrey Olson, Kimberly Hoang, Edjah Nduom, Victor G. Corces, Bing Yao, Steven A. Sloan","doi":"10.1038/s41556-024-01583-9","DOIUrl":"https://doi.org/10.1038/s41556-024-01583-9","url":null,"abstract":"Glioblastoma (GBM) is defined by heterogeneous and resilient cell populations that closely reflect neurodevelopmental cell types. Although it is clear that GBM echoes early and immature cell states, identifying the specific developmental programmes disrupted in these tumours has been hindered by a lack of high-resolution trajectories of glial and neuronal lineages. Here we delineate the course of human astrocyte maturation to uncover discrete developmental stages and attributes mirrored by GBM. We generated a transcriptomic and epigenomic map of human astrocyte maturation using cortical organoids maintained in culture for nearly 2 years. Through this approach, we chronicled a multiphase developmental process. Our time course of human astrocyte maturation includes a molecularly distinct intermediate period that serves as a lineage commitment checkpoint upstream of mature quiescence. This intermediate stage acts as a site of developmental deviation separating IDH-wild-type neoplastic astrocyte-lineage cells from quiescent astrocyte populations. Interestingly, IDH1-mutant tumour astrocyte-lineage cells are the exception to this developmental perturbation, where immature properties are suppressed as a result of d-2-hydroxyglutarate oncometabolite exposure. We propose that this defiance is a consequence of IDH1-mutant-associated epigenetic dysregulation, and we identified biased DNA hydroxymethylation (5hmC) in maturation genes as a possible mechanism. Together, this study illustrates a distinct cellular state aberration in GBM astrocyte-lineage cells and presents developmental targets for experimental and therapeutic exploration.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936060","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

Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint 染色体错分离通过机械敏感的核膜检查点触发细胞周期阻滞

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01565-x

Solène Hervé, Andrea Scelfo, Gabriele Bersano Marchisio, Marine Grison, Kotryna Vaidžiulytė, Marie Dumont, Annapaola Angrisani, Adib Keikhosravi, Gianluca Pegoraro, Mathieu Deygas, Guilherme P. F. Nader, Anne-Sophie Macé, Matteo Gentili, Alice Williart, Nicolas Manel, Matthieu Piel, Yekaterina A. Miroshnikova, Daniele Fachinetti

{"title":"Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint","authors":"Solène Hervé, Andrea Scelfo, Gabriele Bersano Marchisio, Marine Grison, Kotryna Vaidžiulytė, Marie Dumont, Annapaola Angrisani, Adib Keikhosravi, Gianluca Pegoraro, Mathieu Deygas, Guilherme P. F. Nader, Anne-Sophie Macé, Matteo Gentili, Alice Williart, Nicolas Manel, Matthieu Piel, Yekaterina A. Miroshnikova, Daniele Fachinetti","doi":"10.1038/s41556-024-01565-x","DOIUrl":"10.1038/s41556-024-01565-x","url":null,"abstract":"Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear. Here, using a tunable system of chromosome mis-segregation, we show that mitotic errors trigger nuclear deformation, nuclear softening, and lamin and heterochromatin alterations, leading to rapid p53/p21 activation upon mitotic exit in response to changes in nuclear mechanics. We identify mTORC2 and ATR as nuclear deformation sensors upstream of p53/p21 activation. While triggering mitotic arrest, the chromosome mis-segregation-induced alterations of nuclear envelope mechanics provide a fitness advantage for aneuploid cells by promoting nuclear deformation resilience and enhancing pro-invasive capabilities. Collectively, this work identifies a nuclear mechanical checkpoint triggered by altered chromatin organization that probably plays a critical role in cellular transformation and cancer progression. Hervé, Scelfo et al. show that chromosome mis-segregation induces mTORC2- and ATR-mediated p53 activation through a mechanosensitive checkpoint at the nuclear envelope triggered by altered heterochromatin content and increased nuclear membrane tension.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":"73-86"},"PeriodicalIF":17.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01565-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936063","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

FAT1 alterations contribute to chromosomal instability in cancer cells FAT1的改变有助于癌细胞的染色体不稳定性

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-08 DOI: 10.1038/s41556-024-01559-9

引用次数: 0

Mitochondrial YME1L1 governs unoccupied protein translocase channels 线粒体YME1L1控制未占用的蛋白质转位酶通道

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-07 DOI: 10.1038/s41556-024-01571-z

Meng-Chieh Hsu, Hiroki Kinefuchi, Linlin Lei, Reika Kikuchi, Koji Yamano, Richard J. Youle

{"title":"Mitochondrial YME1L1 governs unoccupied protein translocase channels","authors":"Meng-Chieh Hsu, Hiroki Kinefuchi, Linlin Lei, Reika Kikuchi, Koji Yamano, Richard J. Youle","doi":"10.1038/s41556-024-01571-z","DOIUrl":"https://doi.org/10.1038/s41556-024-01571-z","url":null,"abstract":"Mitochondrial protein import through the outer and inner membranes is key to mitochondrial biogenesis. Recent studies have explored how cells respond when import is impaired by a variety of different insults. Here, we developed a mammalian import blocking system using dihydrofolate reductase fused to the N terminus of the inner membrane protein MIC60. While stabilization of the dihydrofolate reductase domain by methotrexate inhibited endogenous mitochondrial protein import, it neither activated the transcription factor ATF4, nor was affected by ATAD1 expression or by VCP/p97 inhibition. On the other hand, notably, plugging the channel of translocase of the outer membrane) induced YME1L1, an ATP-dependent protease, to eliminate translocase of the inner membrane (TIM23) channel components TIMM17A and TIMM23. The data suggest that unoccupied TIM23 complexes expose a C-terminal degron on TIMM17A to YME1L1 for degradation. Import plugging caused a cell growth defect and loss of YME1L1 exacerbated the growth inhibition, showing the protective effect of YME1L1 activity. YME1L1 seems to play a crucial role in mitochondrial quality control to counteract precursor stalling in the translocase of the outer membrane complex and unoccupied TIM23 channels.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"30 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934769","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

Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy 起始枢纽在货物上的相分离是选择性自噬的触发开关

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-01-07 DOI: 10.1038/s41556-024-01572-y

Mariya Licheva, Jeremy Pflaum, Riccardo Babic, Hector Mancilla, Jana Elsässer, Emily Boyle, David M. Hollenstein, Jorge Jimenez-Niebla, Jonas Pleyer, Mio Heinrich, Franz-Georg Wieland, Joachim Brenneisen, Christopher Eickhorst, Johann Brenner, Shan Jiang, Markus Hartl, Sonja Welsch, Carola Hunte, Jens Timmer, Florian Wilfling, Claudine Kraft

{"title":"Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy","authors":"Mariya Licheva, Jeremy Pflaum, Riccardo Babic, Hector Mancilla, Jana Elsässer, Emily Boyle, David M. Hollenstein, Jorge Jimenez-Niebla, Jonas Pleyer, Mio Heinrich, Franz-Georg Wieland, Joachim Brenneisen, Christopher Eickhorst, Johann Brenner, Shan Jiang, Markus Hartl, Sonja Welsch, Carola Hunte, Jens Timmer, Florian Wilfling, Claudine Kraft","doi":"10.1038/s41556-024-01572-y","DOIUrl":"https://doi.org/10.1038/s41556-024-01572-y","url":null,"abstract":"Autophagy is a key cellular quality control mechanism. Nutrient stress triggers bulk autophagy, which nonselectively degrades cytoplasmic material upon formation and liquid–liquid phase separation of the autophagy-related gene 1 (Atg1) complex. In contrast, selective autophagy eliminates protein aggregates, damaged organelles and other cargoes that are targeted by an autophagy receptor. Phase separation of cargo has been observed, but its regulation and impact on selective autophagy are poorly understood. Here, we find that key autophagy biogenesis factors phase separate into initiation hubs at cargo surfaces in yeast, subsequently maturing into sites that drive phagophore nucleation. This phase separation is dependent on multivalent, low-affinity interactions between autophagy receptors and cargo, creating a dynamic cargo surface. Notably, high-affinity interactions between autophagy receptors and cargo complexes block initiation hub formation and autophagy progression. Using these principles, we converted the mammalian reovirus nonstructural protein µNS, which accumulates as particles in the yeast cytoplasm that are not degraded, into a neo-cargo that is degraded by selective autophagy. We show that initiation hubs also form on the surface of different cargoes in human cells and are key to establish the connection to the endoplasmic reticulum, where the phagophore assembly site is formed to initiate phagophore biogenesis. Overall, our findings suggest that regulated phase separation underscores the initiation of both bulk and selective autophagy in evolutionarily diverse organisms.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"48 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934552","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