The EMBO Journal最新文献_第4页

Systematic mapping of mitochondrial calcium uniporter channel (MCUC)-mediated calcium signaling networks. 线粒体钙离子通道（MCUC）介导的钙信号网络系统图。

The EMBO Journal Pub Date : 2024-09-11 DOI: 10.1038/s44318-024-00219-w

Hilda Delgado de la Herran,Denis Vecellio Reane,Yiming Cheng,Máté Katona,Fabian Hosp,Elisa Greotti,Jennifer Wettmarshausen,Maria Patron,Hermine Mohr,Natalia Prudente de Mello,Margarita Chudenkova,Matteo Gorza,Safal Walia,Michael Sheng-Fu Feng,Anja Leimpek,Dirk Mielenz,Natalia S Pellegata,Thomas Langer,György Hajnóczky,Matthias Mann,Marta Murgia,Fabiana Perocchi

{"title":"Systematic mapping of mitochondrial calcium uniporter channel (MCUC)-mediated calcium signaling networks.","authors":"Hilda Delgado de la Herran,Denis Vecellio Reane,Yiming Cheng,Máté Katona,Fabian Hosp,Elisa Greotti,Jennifer Wettmarshausen,Maria Patron,Hermine Mohr,Natalia Prudente de Mello,Margarita Chudenkova,Matteo Gorza,Safal Walia,Michael Sheng-Fu Feng,Anja Leimpek,Dirk Mielenz,Natalia S Pellegata,Thomas Langer,György Hajnóczky,Matthias Mann,Marta Murgia,Fabiana Perocchi","doi":"10.1038/s44318-024-00219-w","DOIUrl":"https://doi.org/10.1038/s44318-024-00219-w","url":null,"abstract":"The mitochondrial calcium uniporter channel (MCUC) mediates mitochondrial calcium entry, regulating energy metabolism and cell death. Although several MCUC components have been identified, the molecular basis of mitochondrial calcium signaling networks and their remodeling upon changes in uniporter activity have not been assessed. Here, we map the MCUC interactome under resting conditions and upon chronic loss or gain of mitochondrial calcium uptake. We identify 89 high-confidence interactors that link MCUC to several mitochondrial complexes and pathways, half of which are associated with human disease. As a proof-of-concept, we validate the mitochondrial intermembrane space protein EFHD1 as a binding partner of the MCUC subunits MCU, EMRE, and MCUB. We further show a MICU1-dependent inhibitory effect of EFHD1 on calcium uptake. Next, we systematically survey compensatory mechanisms and functional consequences of mitochondrial calcium dyshomeostasis by analyzing the MCU interactome upon EMRE, MCUB, MICU1, or MICU2 knockdown. While silencing EMRE reduces MCU interconnectivity, MCUB loss-of-function leads to a wider interaction network. Our study provides a comprehensive and high-confidence resource to gain insights into players and mechanisms regulating mitochondrial calcium signaling and their relevance in human diseases.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TNFSF14+ natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence. TNFSF14+ 自然杀伤细胞通过限制亮氨酸介导的蜕膜基质细胞衰老来防止自然流产。

The EMBO Journal Pub Date : 2024-09-11 DOI: 10.1038/s44318-024-00220-3

Jia-Wei Shi,Zhen-Zhen Lai,Wen-Jie Zhou,Hui-Li Yang,Tao Zhang,Jian-Song Sun,Jian-Yuan Zhao,Ming-Qing Li

{"title":"TNFSF14+ natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence.","authors":"Jia-Wei Shi,Zhen-Zhen Lai,Wen-Jie Zhou,Hui-Li Yang,Tao Zhang,Jian-Song Sun,Jian-Yuan Zhao,Ming-Qing Li","doi":"10.1038/s44318-024-00220-3","DOIUrl":"https://doi.org/10.1038/s44318-024-00220-3","url":null,"abstract":"In preparation for a potential pregnancy, the endometrium of the uterus changes into a temporary structure called the decidua. Senescent decidual stromal cells (DSCs) are enriched in the decidua during decidualization, but the underlying mechanisms of this process remain unclear. Here, we performed single-cell RNA transcriptomics on ESCs and DSCs and found that cell senescence during decidualization is accompanied by increased levels of the branched-chain amino acid (BCAA) transporter SLC3A2. Depletion of leucine, one of the branched-chain amino acids, from cultured media decreased senescence, while high leucine diet resulted in increased senescence and high rates of embryo loss in mice. BCAAs induced senescence in DSCs via the p38 MAPK pathway. In contrast, TNFSF14+ decidual natural killer (dNK) cells were found to inhibit DSC senescence by interacting with its ligand TNFRSF14. As in mice fed high-leucine diets, both mice with NK cell depletion and Tnfrsf14-deficient mice with excessive uterine senescence experienced adverse pregnancy outcomes. Further, we found excessive uterine senescence, SLC3A2-mediated BCAA intake, and insufficient TNFRSF14 expression in the decidua of patients with recurrent spontaneous abortion. In summary, this study suggests that dNK cells maintain senescence homeostasis of DSCs via TNFSF14/TNFRSF14, providing a potential therapeutic strategy to prevent DSC senescence-associated spontaneous abortion.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nitrogen signaling factor triggers a respiration-like gene expression program in fission yeast. 氮信号因子触发裂殖酵母呼吸样基因表达程序

The EMBO Journal Pub Date : 2024-09-10 DOI: 10.1038/s44318-024-00224-z

Shin Ohsawa,Michaela Schwaiger,Vytautas Iesmantavicius,Rio Hashimoto,Hiromitsu Moriyama,Hiroaki Matoba,Go Hirai,Mikiko Sodeoka,Atsushi Hashimoto,Akihisa Matsuyama,Minoru Yoshida,Yoko Yashiroda,Marc Bühler

引用次数: 0

Heteroplasmy in action: tracking mtDNA segregation dynamics. 行动中的杂交：跟踪 mtDNA 的分离动态。

The EMBO Journal Pub Date : 2024-09-10 DOI: 10.1038/s44318-024-00226-x

Nitish Dua,Anjana Badrinarayanan

引用次数: 0

The global phosphorylation landscape of mouse oocytes during meiotic maturation. 小鼠卵母细胞减数分裂成熟过程中的全局磷酸化图谱

The EMBO Journal Pub Date : 2024-09-10 DOI: 10.1038/s44318-024-00222-1

Hongzheng Sun,Longsen Han,Yueshuai Guo,Huiqing An,Bing Wang,Xiangzheng Zhang,Jiashuo Li,Yingtong Jiang,Yue Wang,Guangyi Sun,Shuai Zhu,Shoubin Tang,Juan Ge,Minjian Chen,Xuejiang Guo,Qiang Wang

{"title":"The global phosphorylation landscape of mouse oocytes during meiotic maturation.","authors":"Hongzheng Sun,Longsen Han,Yueshuai Guo,Huiqing An,Bing Wang,Xiangzheng Zhang,Jiashuo Li,Yingtong Jiang,Yue Wang,Guangyi Sun,Shuai Zhu,Shoubin Tang,Juan Ge,Minjian Chen,Xuejiang Guo,Qiang Wang","doi":"10.1038/s44318-024-00222-1","DOIUrl":"https://doi.org/10.1038/s44318-024-00222-1","url":null,"abstract":"Phosphorylation is a key post-translational modification regulating protein function and biological outcomes. However, the phosphorylation dynamics orchestrating mammalian oocyte development remains poorly understood. In the present study, we apply high-resolution mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of mouse oocyte phosphorylation. Of more than 8000 phosphosites, 75% significantly oscillate and 64% exhibit marked upregulation during meiotic maturation, indicative of the dominant regulatory role. Moreover, we identify numerous novel phosphosites on oocyte proteins and a few highly conserved phosphosites in oocytes from different species. Through functional perturbations, we demonstrate that phosphorylation status of specific sites participates in modulating critical events including metabolism, translation, and RNA processing during meiosis. Finally, we combine inhibitor screening and enzyme-substrate network prediction to discover previously unexplored kinases and phosphatases that are essential for oocyte maturation. In sum, our data define landscape of the oocyte phosphoproteome, enabling in-depth mechanistic insights into developmental control of germ cells.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis for the type I-F Cas8-HNH system. I-F 型 Cas8-HNH 系统的结构基础。

The EMBO Journal Pub Date : 2024-09-09 DOI: 10.1038/s44318-024-00229-8

Xuzichao Li,Yanan Liu,Jie Han,Lingling Zhang,Zhikun Liu,Lin Wang,Shuqin Zhang,Qian Zhang,Pengyu Fu,Hang Yin,Hongtao Zhu,Heng Zhang

{"title":"Structural basis for the type I-F Cas8-HNH system.","authors":"Xuzichao Li,Yanan Liu,Jie Han,Lingling Zhang,Zhikun Liu,Lin Wang,Shuqin Zhang,Qian Zhang,Pengyu Fu,Hang Yin,Hongtao Zhu,Heng Zhang","doi":"10.1038/s44318-024-00229-8","DOIUrl":"https://doi.org/10.1038/s44318-024-00229-8","url":null,"abstract":"The Cas3 nuclease is utilized by canonical type I CRISPR-Cas systems for processive target DNA degradation, while a newly identified type I-F CRISPR variant employs an HNH nuclease domain from the natural fusion Cas8-HNH protein for precise target cleavage both in vitro and in human cells. Here, we report multiple cryo-electron microscopy structures of the type I-F Cas8-HNH system at different functional states. The Cas8-HNH Cascade complex adopts an overall G-shaped architecture, with the HNH domain occupying the C-terminal helical bundle domain (HB) of the Cas8 protein in canonical type I systems. The Linker region connecting Cas8-NTD and HNH domains adopts a rigid conformation and interacts with the Cas7.6 subunit, enabling the HNH domain to be in a functional position. The full R-loop formation displaces the HNH domain away from the Cas6 subunit, thus activating the target DNA cleavage. Importantly, our results demonstrate that precise target cleavage is dictated by a C-terminal helix of the HNH domain. Together, our work not only delineates the structural basis for target recognition and activation of the type I-F Cas8-HNH system, but also guides further developments leveraging this system for precise DNA editing.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular mechanism of allosteric activation of the CRISPR ribonuclease Csm6 by cyclic tetra-adenylate 环四腺苷酸异位激活 CRISPR 核糖核酸酶 Csm6 的分子机制

The EMBO Journal Pub Date : 2023-12-19 DOI: 10.1038/s44318-023-00017-w

Liyang Du, Qinwei Zhu, Zhonghui Lin

引用次数: 0

The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover ER膜蛋白复合体通过控制BNIP3的周转限制有丝分裂

The EMBO Journal Pub Date : 2023-12-15 DOI: 10.1038/s44318-023-00006-z

Jose M Delgado, Logan Wallace Shepard, Sarah W Lamson, Samantha L Liu, Christopher J Shoemaker

引用次数: 0

Dynamic coupling of fast channel gating with slow ATP-turnover underpins protein transport through the Sec translocon 快速通道门控与慢速 ATP 翻转的动态耦合是蛋白质通过 Sec 易位子转运的基础

The EMBO Journal Pub Date : 2023-12-15 DOI: 10.1038/s44318-023-00004-1

Joel A. Crossley, W. Allen, Daniel W. Watkins, T. Sabir, S. Radford, Roman Tuma, I. Collinson, Tomas Fessl