EMBO Journal最新文献_第3页

S-palmitoylation modulates ATG2-dependent non-vesicular lipid transport during starvation-induced autophagy. 在饥饿诱导的自噬过程中，S-棕榈酰化可调节 ATG2 依赖性非囊泡脂质转运。

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-24 DOI: 10.1038/s44318-025-00410-7

Wenhui Zheng, Maomao Pu, Sai Zeng, Hongtao Zhang, Qian Wang, Tao Chen, Tianhua Zhou, Chunmei Chang, Dante Neculai, Wei Liu

{"title":"S-palmitoylation modulates ATG2-dependent non-vesicular lipid transport during starvation-induced autophagy.","authors":"Wenhui Zheng, Maomao Pu, Sai Zeng, Hongtao Zhang, Qian Wang, Tao Chen, Tianhua Zhou, Chunmei Chang, Dante Neculai, Wei Liu","doi":"10.1038/s44318-025-00410-7","DOIUrl":"10.1038/s44318-025-00410-7","url":null,"abstract":"Lipid transfer proteins mediate the non-vesicular transport of lipids at membrane contact sites to regulate the lipid composition of organelle membranes. Despite significant recent advances in our understanding of the structural basis for lipid transfer, its functional regulation remains unclear. In this study, we report that S-palmitoylation modulates the cellular function of ATG2, a rod-like lipid transfer protein responsible for transporting phospholipids from the endoplasmic reticulum (ER) to phagophores during autophagosome formation. During starvation-induced autophagy, ATG2A undergoes depalmitoylation as the balance between ZDHHC11-mediated palmitoylation and APT1-mediated depalmitoylation. Inhibition of ATG2A depalmitoylation leads to impaired autophagosome formation and disrupted autophagic flux. Further, in cell and in vitro analyses demonstrate that S-palmitoylation at the C-terminus of ATG2A anchors the C-terminus to the ER. Depalmitoylation detaches the C-terminus from the ER membrane, enabling it to interact with phagophores and promoting their growth. These findings elucidate a S-palmitoylation-dependent regulatory mechanism of cellular ATG2, which may represent a broad regulatory strategy for lipid transport mediated by bridge-like transporters within cells.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701978","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

A new hybrid post-translational modification-have you lost your (MARUb)les?

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-20 DOI: 10.1038/s44318-025-00413-4

Isaac de Araujo Matos, Nícolas Carlos Hoch

引用次数: 0

Author Correction: Drosophila Alms1 proteins regulate centriolar cartwheel assembly by enabling Plk4-Ana2 amplification loop.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-18 DOI: 10.1038/s44318-025-00411-6

Marine Brunet, Joëlle Thomas, Jean-André Lapart, Léo Krüttli, Marine H Laporte, Maria Giovanna Riparbelli, Giuliano Callaini, Bénédicte Durand, Véronique Morel

引用次数: 0

Nanoscale analysis of human G1 and metaphase chromatin in situ.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-17 DOI: 10.1038/s44318-025-00407-2

Jon Ken Chen, Tingsheng Liu, Shujun Cai, Weimei Ruan, Cai Tong Ng, Jian Shi, Uttam Surana, Lu Gan

引用次数: 0

An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-13 DOI: 10.1038/s44318-025-00408-1

Alireza Ghanbarpour, Bertina Telusma, Barrett M Powell, Jia Jia Zhang, Isabella Bolstad, Carolyn Vargas, Sandro Keller, Tania A Baker, Robert T Sauer, Joseph H Davis

{"title":"An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins.","authors":"Alireza Ghanbarpour, Bertina Telusma, Barrett M Powell, Jia Jia Zhang, Isabella Bolstad, Carolyn Vargas, Sandro Keller, Tania A Baker, Robert T Sauer, Joseph H Davis","doi":"10.1038/s44318-025-00408-1","DOIUrl":"10.1038/s44318-025-00408-1","url":null,"abstract":"The AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into the periplasm of E. coli. How this bacterial complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear. Following the overproduction of protein components, recent cryo-EM structures showed symmetric HflK/C cages surrounding FtsH in a manner proposed to inhibit the degradation of membrane-embedded substrates. Here, we present structures of native protein complexes, in which HflK/C instead forms an asymmetric nautilus-shaped assembly with an entryway for membrane-embedded substrates to reach and be engaged by FtsH. Consistent with this nautilus-like structure, proteomic assays suggest that HflK/C enhances FtsH degradation of certain membrane-embedded substrates. Membrane curvature in our FtsH•HflK/C complexes is opposite that of surrounding membrane regions, a property that correlates with lipid scramblase activity and possibly with FtsH's function in the degradation of membrane-embedded proteins.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626663","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

A versatile toolbox for determining IRES activity in cells and embryonic tissues.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-13 DOI: 10.1038/s44318-025-00404-5

Philipp Koch, Zijian Zhang, Naomi R Genuth, Teodorus Theo Susanto, Martin Haimann, Alena Khmelinskaia, Gun Woo Byeon, Saurabh Dey, Maria Barna, Kathrin Leppek

{"title":"A versatile toolbox for determining IRES activity in cells and embryonic tissues.","authors":"Philipp Koch, Zijian Zhang, Naomi R Genuth, Teodorus Theo Susanto, Martin Haimann, Alena Khmelinskaia, Gun Woo Byeon, Saurabh Dey, Maria Barna, Kathrin Leppek","doi":"10.1038/s44318-025-00404-5","DOIUrl":"https://doi.org/10.1038/s44318-025-00404-5","url":null,"abstract":"Widespread control of gene expression through translation has emerged as a key level of spatiotemporal regulation of protein expression. A prominent mechanism by which ribosomes can confer gene regulation is via internal ribosomal entry sites (IRESes), whose functions have however, remained difficult to rigorously characterize. Here we present a set of technologies in embryos and cells, including IRES-mediated translation of circular RNA (circRNA) reporters, single-molecule messenger (m)RNA isoform imaging, PacBio long-read sequencing, and isoform-sensitive mRNA quantification along polysome profiles as a new toolbox for understanding IRES regulation. Using these techniques, we investigate a broad range of cellular IRES RNA elements including Hox IRESes. We show IRES-dependent translation in circRNAs, as well as the relative expression, localization, and translation of an IRES-containing mRNA isoform in specific embryonic tissues. We thereby provide a new resource of technologies to elucidate the roles of versatile IRES elements in gene regulation and embryonic development.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626659","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

Surface-mediated bacteriophage defense incurs fitness tradeoffs for interbacterial antagonism.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-10 DOI: 10.1038/s44318-025-00406-3

Chia-En Tsai, Feng-Qi Wang, Chih-Wen Yang, Ling-Li Yang, Thao Vp Nguyen, Yung-Chih Chen, Po-Yin Chen, Ing-Shouh Hwang, See-Yeun Ting

{"title":"Surface-mediated bacteriophage defense incurs fitness tradeoffs for interbacterial antagonism.","authors":"Chia-En Tsai, Feng-Qi Wang, Chih-Wen Yang, Ling-Li Yang, Thao Vp Nguyen, Yung-Chih Chen, Po-Yin Chen, Ing-Shouh Hwang, See-Yeun Ting","doi":"10.1038/s44318-025-00406-3","DOIUrl":"https://doi.org/10.1038/s44318-025-00406-3","url":null,"abstract":"Bacteria in polymicrobial habitats are constantly exposed to biotic threats from bacteriophages (or \"phages\"), antagonistic bacteria, and predatory eukaryotes. These antagonistic interactions play crucial roles in shaping the evolution and physiology of bacteria. To survive, bacteria have evolved mechanisms to protect themselves from such attacks, but the fitness costs of resisting one threat and rendering bacteria susceptible to others remain unappreciated. Here, we examined the fitness consequences of phage resistance in Salmonella enterica, revealing that phage-resistant variants exhibited significant fitness loss upon co-culture with competitor bacteria. These phage-resistant strains display varying degrees of lipopolysaccharide (LPS) deficiency and increased susceptibility to contact-dependent interbacterial antagonism, such as the type VI secretion system (T6SS). Utilizing mutational analyses and atomic force microscopy, we show that the long-modal length O-antigen of LPS serves as a protective barrier against T6SS-mediated intoxication. Notably, this competitive disadvantage can also be triggered independently by phages possessing LPS-targeting endoglycosidase in their tail spike proteins, which actively cleave the O-antigen upon infection. Our findings reveal two distinct mechanisms of phage-mediated LPS modifications that modulate interbacterial competition, shedding light on the dynamic microbial interplay within mixed populations.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598323","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

Mitochondrial fatty acid oxidation regulates adult muscle stem cell function through modulating metabolic flux and protein acetylation.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-10 DOI: 10.1038/s44318-025-00397-1

Feng Yue, Lijie Gu, Jiamin Qiu, Stephanie N Oprescu, Linda M Beckett, Jessica M Ellis, Shawn S Donkin, Shihuan Kuang

{"title":"Mitochondrial fatty acid oxidation regulates adult muscle stem cell function through modulating metabolic flux and protein acetylation.","authors":"Feng Yue, Lijie Gu, Jiamin Qiu, Stephanie N Oprescu, Linda M Beckett, Jessica M Ellis, Shawn S Donkin, Shihuan Kuang","doi":"10.1038/s44318-025-00397-1","DOIUrl":"https://doi.org/10.1038/s44318-025-00397-1","url":null,"abstract":"During homeostasis and regeneration, satellite cells, the resident stem cells of skeletal muscle, have distinct metabolic requirements for fate transitions between quiescence, proliferation and differentiation. However, the contribution of distinct energy sources to satellite cell metabolism and function remains largely unexplored. Here, we uncover a role of mitochondrial fatty acid oxidation (FAO) in satellite cell integrity and function. Single-cell RNA sequencing revealed progressive enrichment of mitochondrial FAO and downstream pathways during activation, proliferation and myogenic commitment of satellite cells. Deletion of Carnitine palmitoyltransferase 2 (Cpt2), the rate-limiting enzyme in FAO, hampered muscle stem cell expansion and differentiation upon acute muscle injury, markedly delaying regeneration. Cpt2 deficiency reduces acetyl-CoA levels in satellite cells, impeding the metabolic flux and acetylation of selective proteins including Pax7, the central transcriptional regulator of satellite cells. Notably, acetate supplementation restored cellular metabolic flux and partially rescued the regenerative defects of Cpt2-null satellite cells. These findings highlight an essential role of fatty acid oxidation in controlling satellite cell function and suggest an integration of lipid metabolism and protein acetylation in adult stem cells.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598320","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

Slik sculpts the plasma membrane into cytonemes to control cell-cell communication.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-06 DOI: 10.1038/s44318-025-00401-8

Basile Rambaud, Mathieu Joseph, Feng-Ching Tsai, Camille De Jamblinne, Regina Strakhova, Emmanuelle Del Guidice, Renata Sabelli, Matthew J Smith, Patricia Bassereau, David R Hipfner, Sébastien Carréno

{"title":"Slik sculpts the plasma membrane into cytonemes to control cell-cell communication.","authors":"Basile Rambaud, Mathieu Joseph, Feng-Ching Tsai, Camille De Jamblinne, Regina Strakhova, Emmanuelle Del Guidice, Renata Sabelli, Matthew J Smith, Patricia Bassereau, David R Hipfner, Sébastien Carréno","doi":"10.1038/s44318-025-00401-8","DOIUrl":"https://doi.org/10.1038/s44318-025-00401-8","url":null,"abstract":"Cytonemes are signaling filopodia that facilitate long-range cell-cell communication by forming synapses between cells. Initially discovered in Drosophila for transporting morphogens during embryogenesis, they have since been identified in mammalian cells and implicated in carcinogenesis. Despite their importance, mechanisms controlling cytoneme biogenesis remain elusive. Here, we demonstrate that the Ser/Thr kinase Slik drives remote cell proliferation by promoting cytoneme formation. This function depends on the coiled-coil domain of Slik (SlikCCD), which directly sculpts membranes into tubules. Importantly, Slik plays opposing roles in cytoneme biogenesis: its membrane-sculpting activity promotes cytoneme formation, but this is counteracted by its kinase activity, which enhances actin association with the plasma membrane via Moesin phosphorylation. In vivo, SlikCCD enhances cytoneme formation in one epithelial layer of the wing disc to promote cell proliferation in an adjacent layer. Finally, this function relies on the STRIPAK complex, which controls cytoneme formation and governs proliferation at a distance by regulating Slik association with the plasma membrane. Our study unveils an unexpected structural role of a kinase in sculpting membranes, crucial for cytoneme-mediated control of cell proliferation.","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574547","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

A double-agent microRNA regulates viral cross-kingdom infection in animals and plants.

IF 9.4 1区生物学

EMBO Journal Pub Date : 2025-03-05 DOI: 10.1038/s44318-025-00405-4

Wan Zhao, Hong Lu, Jiaming Zhu, Lan Luo, Feng Cui

引用次数: 0