The EMBO Journal最新文献

Mechanistic insights into Bcs1-mediated mitochondrial membrane translocation of the folded Rieske protein. bcs1介导的折叠Rieske蛋白线粒体膜易位的机制。

The EMBO Journal Pub Date : 2025-05-23 DOI: 10.1038/s44318-025-00459-4

Cristian Rosales-Hernandez,Matthias Thoms,Otto Berninghausen,Thomas Becker,Roland Beckmann

{"title":"Mechanistic insights into Bcs1-mediated mitochondrial membrane translocation of the folded Rieske protein.","authors":"Cristian Rosales-Hernandez,Matthias Thoms,Otto Berninghausen,Thomas Becker,Roland Beckmann","doi":"10.1038/s44318-025-00459-4","DOIUrl":"https://doi.org/10.1038/s44318-025-00459-4","url":null,"abstract":"A functional mitochondrial respiratory chain requires coordinated and tightly regulated assembly of mitochondrial- and nuclear-encoded subunits. For bc1 complex (complex III) assembly, the iron-sulfur protein Rip1 must first be imported into the mitochondrial matrix to fold and acquire its 2Fe-2S cluster, then translocated and inserted into the inner mitochondrial membrane (IM). This translocation of folded Rip1 is accomplished by Bcs1, an unusual heptameric AAA ATPase that couples ATP hydrolysis to translocation. However, the molecular and mechanistic details of Bcs1-mediated Rip1 translocation have remained elusive. Here, we provide structural and biochemical evidence on how Bcs1 alternates between conformational states to translocate Rip1 across the IM. Using cryo-electron microscopy (cryo-EM), we identified substrate-bound pre-translocation and pre-release states, revealing how electrostatic interactions promote Rip1 binding to Bcs1. An ATP-induced conformational switch of the Bcs1 heptamer facilitates Rip1 translocation between two distinct aqueous vestibules-one exposed to the matrix, the other to the intermembrane space-in an airlock-like mechanism. This would minimize disruption of the IM permeability barrier, which could otherwise lead to proton leakage and compromised mitochondrial energy conversion.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130724","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

Translocation of gut bacteria promotes tumor-associated mortality by inducing immune-activated renal damage. 肠道细菌的易位通过诱导免疫激活的肾脏损伤促进肿瘤相关的死亡。

The EMBO Journal Pub Date : 2025-05-22 DOI: 10.1038/s44318-025-00458-5

Fei Cong,Hongcun Bao,Xianfeng Wang,Yang Tang,Yuwei Bao,John S Poulton,Xiaowen Liu,Adam Chun-Nin Wong,Xiang Ji,Wu-Min Deng

{"title":"Translocation of gut bacteria promotes tumor-associated mortality by inducing immune-activated renal damage.","authors":"Fei Cong,Hongcun Bao,Xianfeng Wang,Yang Tang,Yuwei Bao,John S Poulton,Xiaowen Liu,Adam Chun-Nin Wong,Xiang Ji,Wu-Min Deng","doi":"10.1038/s44318-025-00458-5","DOIUrl":"https://doi.org/10.1038/s44318-025-00458-5","url":null,"abstract":"Paraneoplastic syndrome represents severe and complex systemic clinical symptoms manifesting in multiple organs of cancer patients, but its cause and cellular underpinnings remain little explored. In this study, establishing a Drosophila model of paraneoplastic syndrome triggered by tumor transplantation, we found that the innate immune response, initiated by translocated commensal bacteria from a compromised intestine, significantly contributes to reduced lifespan in tumor-bearing hosts. Our data identify the renal system as a central hub of this paraneoplastic syndrome model, wherein the pericardial nephrocytes undergo severe damage due to an elevated immune response triggered by gut dysbiosis and bacterial translocation. This innate immune response-induced nephrocyte damage is a major contributor to reduced longevity in tumor-bearing hosts, as blocking the NF-kB/Imd pathway in nephrocytes or removing gut bacteria via germ-free derivation or antibiotic treatment ameliorates nephrocyte deterioration and extends the lifespan of tumor-bearing flies. Consistently, treatment with a detoxifying drug also extended the lifespan of the tumor hosts. Our findings highlight a critical role of the gut-kidney axis in the paraneoplastic complications observed in cancer-bearing flies, suggesting potential therapeutic targets for mitigating similar complications in cancer patients.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"59 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122153","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

Inflammatory crosstalk: systemic gut-kidney interplay aggravates tumor host mortality. 炎症串扰：全身性肠肾相互作用加重肿瘤宿主死亡率。

The EMBO Journal Pub Date : 2025-05-22 DOI: 10.1038/s44318-025-00457-6

Héctor Herranz

引用次数: 0

Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence. 氧需要硫，硫需要氧：一种相互依赖的关系。

The EMBO Journal Pub Date : 2025-05-20 DOI: 10.1038/s44318-025-00464-7

Hiroki Sekine,Takaaki Akaike,Hozumi Motohashi

{"title":"Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.","authors":"Hiroki Sekine,Takaaki Akaike,Hozumi Motohashi","doi":"10.1038/s44318-025-00464-7","DOIUrl":"https://doi.org/10.1038/s44318-025-00464-7","url":null,"abstract":"Oxygen and sulfur, both members of the chalcogen group (group 16 elements), play fundamental roles in life. Ancient organisms primarily utilized sulfur for energy metabolism, while the rise in atmospheric oxygen facilitated the evolution of aerobic organisms, enabling highly efficient energy production. Nevertheless, all modern organisms, both aerobes and anaerobes, must protect themselves from oxygen toxicity. Interestingly, aerobes still rely on sulfur for survival. This dependence has been illuminated by the recent discovery of supersulfides, a novel class of biomolecules, made possible through advancements in technology and analytical methods. These breakthroughs are reshaping our understanding of biological processes and emphasizing the intricate interplay between oxygen and sulfur in regulating essential redox reactions. This review summarizes the latest insights into the biological roles of sulfur and oxygen, their interdependence in key processes, and their contributions to adaptive responses to environmental stressors. By exploring these interactions, we aim to provide a comprehensive perspective on how these elements drive survival strategies across diverse life forms, highlighting their indispensable roles in both human health and the sustenance of life.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103898","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

Redox regulation of G protein oligomerization and signaling by the glutaredoxin WG1 controls grain size in rice. 谷氨酰胺还毒素WG1对水稻G蛋白寡聚和信号传导的氧化还原调控。

The EMBO Journal Pub Date : 2025-05-19 DOI: 10.1038/s44318-025-00462-9

Lijie Liu,Jianqin Hao,Ke Huang,Penggen Duan,Baolan Zhang,Zhihai Chi,Xiaohong Yao,Yunhai Li

{"title":"Redox regulation of G protein oligomerization and signaling by the glutaredoxin WG1 controls grain size in rice.","authors":"Lijie Liu,Jianqin Hao,Ke Huang,Penggen Duan,Baolan Zhang,Zhihai Chi,Xiaohong Yao,Yunhai Li","doi":"10.1038/s44318-025-00462-9","DOIUrl":"https://doi.org/10.1038/s44318-025-00462-9","url":null,"abstract":"Grain size is an important agronomic trait and influences both grain yield and quality in crops. The atypical heterotrimeric Gγ protein subunit GS3 is a central regulator of grain length in rice, and the loss-of-function allele of its corresponding gene has been widely utilized by breeders to improve grain length in rice. Here we report that the CC-type glutaredoxin WG1/OsGRX8 has disulfide oxidoreductase activity and regulates redox state of GS3, thereby determining grain length in rice. GS3 can form dimers and oligomers by intermolecular disulfide bonds, and the cysteine-rich C-terminal region of GS3 is predominantly required for its oligomerization. The oligomerization of GS3 alleviates its inhibitory effect on the interaction between RGB1 and DEP1/GGC2, resulting in an increase in grain length. WG1 interacts with GS3 and reduces the oligomerization of GS3 through redox mechanisms, which causes a decrease in grain length. Genetic analyses support WG1 and GS3 function in a common pathway to control grain length. Thus, our findings reveal a previously unrecognized mechanism, in which redox regulation of a Gγ subunit by a glutaredoxin controls grain length, opening a novel perspective for G protein signaling regulation.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097770","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

Early coordination of cell migration and cardiac fate determination during mammalian gastrulation. 哺乳动物原肠胚形成过程中细胞迁移和心脏命运决定的早期协调。

The EMBO Journal Pub Date : 2025-05-13 DOI: 10.1038/s44318-025-00441-0

Shayma Abukar,Peter A Embacher,Alessandro Ciccarelli,Sunita Varsani-Brown,Isabel G W North,Jamie A Dean,James Briscoe,Kenzo Ivanovitch

{"title":"Early coordination of cell migration and cardiac fate determination during mammalian gastrulation.","authors":"Shayma Abukar,Peter A Embacher,Alessandro Ciccarelli,Sunita Varsani-Brown,Isabel G W North,Jamie A Dean,James Briscoe,Kenzo Ivanovitch","doi":"10.1038/s44318-025-00441-0","DOIUrl":"https://doi.org/10.1038/s44318-025-00441-0","url":null,"abstract":"During gastrulation, mesodermal cells derived from distinct regions are destined to acquire specific cardiac fates after undergoing complex migratory movements. Here, we used light-sheet imaging of live mouse embryos between gastrulation and heart tube formation to track mesodermal cells and to reconstruct lineage trees and 3D migration paths for up to five cell divisions. We found independent progenitors emerging at specific times, contributing exclusively to left ventricle/atrioventricular canal (LV/AVC) or atrial myocytes. LV/AVC progenitors differentiated early to form the cardiac crescent, while atrial progenitors later generated the heart tube's Nr2f2+ inflow tract during morphogenesis. We also identified short-lived multipotent progenitors with broad potential, illustrating early developmental plasticity. Descendants of multipotent progenitors displayed greater dispersion and more diverse migratory trajectories within the anterior mesoderm than the progeny of uni-fated progenitors. Progenitors contributing to extraembryonic mesoderm (ExEm) exhibited the fastest and most dispersed migrations. In contrast, those giving rise to endocardial, LV/AVC, and pericardial cells showed a more gradual divergence, with late-stage behavioural shifts: endocardial cells increased in speed, while pericardial cells slowed down in comparison to LV/AVC cells. Together, these data reveal patterns of individual cell directionality and cardiac fate allocation within the seemingly unorganised migratory pattern of mesoderm cells.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945393","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

Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells. 醛缩酶调节的G3BP1/2+凝聚物控制β细胞中胰岛素mRNA的储存。

The EMBO Journal Pub Date : 2025-05-12 DOI: 10.1038/s44318-025-00448-7

Esteban Quezada,Klaus-Peter Knoch,Jovana Vasiljevic,Annika Seiler,Akshaye Pal,Abishek Gunasekaran,Carla Münster,Daniela Friedland,Eyke Schöniger,Anke Sönmez,Pascal Roch,Carolin Wegbrod,Katharina Ganß,Nicole Kipke,Simon Alberti,Rita Nano,Lorenzo Piemonti,Daniela Aust,Jürgen Weitz,Marius Distler,Michele Solimena

{"title":"Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells.","authors":"Esteban Quezada,Klaus-Peter Knoch,Jovana Vasiljevic,Annika Seiler,Akshaye Pal,Abishek Gunasekaran,Carla Münster,Daniela Friedland,Eyke Schöniger,Anke Sönmez,Pascal Roch,Carolin Wegbrod,Katharina Ganß,Nicole Kipke,Simon Alberti,Rita Nano,Lorenzo Piemonti,Daniela Aust,Jürgen Weitz,Marius Distler,Michele Solimena","doi":"10.1038/s44318-025-00448-7","DOIUrl":"https://doi.org/10.1038/s44318-025-00448-7","url":null,"abstract":"Upregulation of insulin mRNA translation upon hyperglycemia in pancreatic islet β-cells involves several RNA-binding proteins. Here, we found that G3BP1, a stress granule marker downregulated in islets of subjects with type 2 diabetes, binds to insulin mRNA in glucose concentration-dependent manner. We show in mouse insulinoma MIN6-K8 cells exposed to fasting glucose levels that G3BP1 and its paralog G3BP2 colocalize to cytosolic condensates with eIF3b, phospho-AMPKαThr172 and Ins1/2 mRNA. Glucose stimulation dissolves G3BP1+/2+ condensates with cytosolic redistribution of their components. The aldolase inhibitor aldometanib prevents the glucose- and pyruvate-induced dissolution of G3BP1+/2+ condensates, increases phospho-AMPKαThr172 levels and reduces those of phospho-mTORSer2448. G3BP1 or G3BP2 depletion precludes condensate assembly. KO of G3BP1 decreases Ins1/2 mRNA abundance and translation as well as proinsulin levels, and impaires glucose-stimulated insulin secretion. Further, other insulin secretagogues such as exendin-4 and palmitate, but not high KCl, prompts the dissolution of G3BP1+/2+ condensates. G3BP1+/2+/Ins mRNA+ condensates are also found in primary mouse and human β-cells. Hence, G3BP1+/2+ condensates represent a conserved glycolysis/aldolase-regulated compartment for the physiological storage and protection of insulin mRNA in resting β-cells.","PeriodicalId":501009,"journal":{"name":"The EMBO Journal","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945067","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

YTHDC1 promotes postnatal brown adipose tissue development and thermogenesis by stabilizing PPARγ. YTHDC1通过稳定PPARγ促进出生后棕色脂肪组织的发育和产热。

The EMBO Journal Pub Date : 2025-05-12 DOI: 10.1038/s44318-025-00460-x

Lihua Wang,Yuqin Wang,Kaixin Ding,Zhenzhi Li,Zhipeng Zhang,Xinzhi Li,Yue Song,Liwei Xie,Zheng Chen

引用次数: 0

Approaches to stable isotope tracing and in vivo metabolomics in the cancer clinic. 稳定同位素示踪和体内代谢组学在癌症临床中的应用。

The EMBO Journal Pub Date : 2025-05-12 DOI: 10.1038/s44318-025-00450-z

Brandon Faubert,Alpaslan Tasdogan

引用次数: 0

Mechanistic insight into anaphase bridge signaling to the abscission checkpoint. 对分离检查点的后期桥接信号机制的洞察。

The EMBO Journal Pub Date : 2025-05-12 DOI: 10.1038/s44318-025-00453-w

Manika I Singh,Girish Rajendraprasad,Vasileios Katopodis,Rui Cui,Marin Barisic,Rahul Bhowmick,Ian D Hickson

引用次数: 0