The FEBS journal最新文献

{"title":"Roles and applications of autophagy in guarding against environmental stress and DNA damage in Saccharomyces cerevisiae.","authors":"Tong Zhang, Yuping Lin, Ziteng Zhang, Zhen Wang, Fanli Zeng, Qinhong Wang","doi":"10.1111/febs.70112","DOIUrl":"https://doi.org/10.1111/febs.70112","url":null,"abstract":"<p><p>Saccharomyces cerevisiae (S. cerevisiae), a famous chassis cell factory, often faces various environmental stress conditions like extreme temperature, osmolarity, and nutrient starvation during the fermentation process. Additionally, chromosomal replication and genome editing-assisted metabolic engineering may cause DNA damage to S. cerevisiae. S. cerevisiae has evolved multiple elaborate mechanisms to fend against these adverse conditions. One of these \"self-repair\" mechanisms is autophagy, a ubiquitous \"self-eating\" mechanism that transports intracellular components to the lysosome/vacuole for degradation. Here, we reviewed the current state of our knowledge about the role and application of autophagy regulation in S. cerevisiae in response to environmental stress and genome damage, which may provide new strategies for developing robust industrial yeast and accelerating genome engineering.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045590","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}

{"title":"Identification of CO-binding modes in the Cu_B site of bovine cytochrome c oxidase by spatial mapping of binding energy.","authors":"Jiyoung Kang, Toru Matsuoka, Masaru Tateno","doi":"10.1111/febs.70115","DOIUrl":"https://doi.org/10.1111/febs.70115","url":null,"abstract":"<p><p>Cytochrome c oxidase (CcO) is the terminal enzyme of the electron-transfer system and reduces an oxygen molecule to two water molecules. The trigger of this reaction is the binding of an oxygen molecule to the binuclear center (BNC) comprising the Cu_B site and heme a₃. Due to the difficulty in obtaining the crystal structure of the complex with an oxygen molecule, other ligand molecules have been utilized to investigate the ligand-binding mechanism. In the previous studies, crystal structures of complexes with CO, NO, and CN^- ligands were determined, suggesting dynamic changes in helix X induced by ligand binding according to time-resolved infrared spectroscopic analysis. In this study, we employed ab initio quantum mechanical calculations to elucidate the ligand-recognition mechanisms of the Cu_B site and systematically analyzed the potential fields comprising the BNC and ligands. Additionally, we evaluated the effect of Tyr244 and Val243 located close to the BNC site on the potential fields, identifying Val243 as a critical factor in determining the configuration of the CO ligand bound to the Cu_B site by inducing hybridization between the 2p orbital of the O atom (CO) and the 3d orbital of the Fe atom (heme a₃). Furthermore, the Val243 model indicated the existence of two CO ligand configurations, which were consistent with experimental Fourier-transform infrared spectroscopy data. To the best of our knowledge, this represents the first elucidation of the functional role of Val243.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000977","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}

{"title":"Transcription-coupled repair: tangled up in convoluted repair.","authors":"Diana A Llerena Schiffmacher, Yun Jin Pai, Alex Pines, Wim Vermeulen","doi":"10.1111/febs.70104","DOIUrl":"https://doi.org/10.1111/febs.70104","url":null,"abstract":"<p><p>Significant progress has been made in understanding the mechanism of transcription-coupled nucleotide excision repair (TC-NER); however, numerous aspects remain elusive, including TC-NER regulation, lesion-specific and cell type-specific complex composition, structural insights, and lesion removal dynamics in living cells. This review summarizes and discusses recent advancements in TC-NER, focusing on newly identified interactors, mechanistic insights from cryo-electron microscopy (Cryo-EM) studies and live cell imaging, and the contribution of post-translational modifications (PTMs), such as ubiquitin, in regulating TC-NER. Furthermore, we elaborate on the consequences of TC-NER deficiencies and address the role of accumulated damage and persistent lesion-stalled RNA polymerase II (Pol II) as major drivers of the disease phenotype of Cockayne syndrome (CS) and its related disorders. In this context, we also discuss the severe effects of transcription-blocking lesions (TBLs) on neurons, highlighting their susceptibility to damage. Lastly, we explore the potential of investigating three-dimensional (3D) chromatin structure and phase separation to uncover further insights into this essential DNA repair pathway.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053172","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}

{"title":"Glucose sensing and the unfolded protein response","authors":"Mabel Cruz-Rodríguez,&nbsp;Eric Chevet,&nbsp;Cristina Muñoz-Pinedo","doi":"10.1111/febs.70113","DOIUrl":"10.1111/febs.70113","url":null,"abstract":"<p>The unfolded protein response (UPR) is activated primarily upon alteration of protein folding in the endoplasmic reticulum (ER). This occurs under physiological situations that cause an abrupt increase in protein synthesis, or under redox and metabolic stresses. Among the latter, hyperglycemia and glucose scarcity have been identified as major modulators of UPR signaling. Indeed, the first mammalian UPR effector, the glucose-regulated protein 78, also known as BiP, was identified in response to glucose deprivation. Tunicamycin, arguably the most commonly used drug to induce ER stress responses <i>in vitro</i> and <i>in vivo</i>, is an inhibitor of <i>N</i>-glycosylation. We compile here evidence that the UPR is activated upon physiological and pathological conditions that alter glucose levels and that this is mostly mediated by alterations of protein <i>N</i>-glycosylation, ATP levels, or redox balance. The three branches of the UPR transduced by PERK/ATF4, IRE1/XBP1s, and ATF6, as well as non-canonical ER sensors such as SCAP/SREBP, sense ER protein glycosylation status driven by glucose and other glucose-derived metabolites. The outcomes of UPR activation range from restoring protein <i>N</i>-glycosylation and protein folding flux to stimulating autophagy, organelle recycling, and mitochondrial respiration, and in some cases, cell death. Anabolic responses to glucose levels are also stimulated by glucose through components of the UPR. Therefore, the UPR should be further studied as a potential biomarker and mediator of glucose-associated diseases.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 14","pages":"3581-3595"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracing the evolutionary pathway: on the origin of mitochondria and eukaryogenesis.","authors":"J Ernesto Bravo-Arévalo","doi":"10.1111/febs.70109","DOIUrl":"https://doi.org/10.1111/febs.70109","url":null,"abstract":"<p><p>The mito-early hypothesis posits that mitochondrial integration was a key driver in the evolution of defining eukaryotic characteristics (DECs). Building on previous work that identified endosymbiotic selective pressures as central to eukaryotic cell evolution, this study examines how endosymbiotic gene transfer (EGT) and the resulting genomic and bioenergetic constraints shaped mitochondrial protein import systems. These systems were crucial for maintaining cellular function in early eukaryotes and facilitated their subsequent diversification. A primary focus is the co-evolution of mitochondrial import mechanisms and eukaryotic endomembrane complexity. Specifically, I investigate how the necessity for nuclear-encoded mitochondrial protein import drove the adaptation of bacterial secretion components, alongside eukaryotic innovations, to refine translocation pathways. Beyond enabling bioenergetic expansion, mitochondrial endosymbiosis played a fundamental role in the emergence of compartmentalisation and cellular complexity in LECA, driving the evolution of organellar networks. By integrating genomic, structural and phylogenetic evidence, this study aimed to contribute to the mito-early framework, clarifying the mechanisms that linked mitochondrial acquisition to the origin of eukaryotic cells.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061150","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}

{"title":"TRS85 and LEM3 suppressor mutations rescue stress hypersensitivities caused by lack of structural diversity of complex sphingolipids in budding yeast.","authors":"Momoko Matsuzaki, Ayano Koga, Satomi Yamagata, Takahiro Kawaguchi, Motohiro Tani","doi":"10.1111/febs.70094","DOIUrl":"https://doi.org/10.1111/febs.70094","url":null,"abstract":"<p><p>The budding yeast Saccharomyces cerevisiae can synthesise 15 subtypes of complex sphingolipids, and this structural diversity is thought to be the molecular basis that enables the range of biological functions of complex sphingolipids. Through analyses of yeast mutants with various deletion combinations of complex-sphingolipid-metabolising enzyme genes (CSG1, CSH1, IPT1, SUR2 and SCS7), it was previously shown that less structural diversity of complex sphingolipids leads to increased sensitivity to multiple environmental stresses, with impaired plasma-membrane and cell-wall integrity. In this study, we screened for suppressor mutations that can alleviate the stress hypersensitivities of csg1Δ csh1Δ sur2Δ scs7Δ (ccssΔ) cells. Mutations of trafficking protein particle complex III-specific subunit 85 (TRS85; encodes a component of the TRAPPIII complex, involved in membrane trafficking) and phospholipid-transporting ATPase Dnf2 (DNF2; encodes the plasma-membrane glycerophospholipid flippase) were identified as suppressor mutations. Loss of Trs85 or phospholipid-transporting ATPase accessory subunit Lem3 (LEM3; encodes a regulatory subunit of Dnf2) differed in the type of stress being conferred resistance to ccss∆ cells. Furthermore, it was also found that impaired plasma-membrane and cell-wall integrities in ccssΔ cells were suppressed by trs85∆ but not lem3∆. Moreover, ccss∆ cells exhibited abnormal localisation of yeGFP-Snc1 in endosomes, which is suppressed by trs85∆ but not lem3∆. Overexpression of GTP-binding protein Ypt1, which is regulated by TRAPPIII and involved in vesicular trafficking, exacerbated plasma-membrane integrity abnormalities and stress sensitivities in ccss∆ cells. Thus, it was suggested that TRS85 and LEM3 deletion confer stress tolerances to ccssΔ cells through distinct mechanisms. These findings will provide insights into the physiological significance of the structural diversity of complex sphingolipids.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039584","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}

{"title":"Oxaliplatin accelerates immunogenic cell death by activating the cGAS/STING/TBK1/IRF5 pathway in gastric cancer","authors":"Siwei Zhao,&nbsp;Dong Sun,&nbsp;Hang Yu,&nbsp;Menglin Wang,&nbsp;Botao Xu,&nbsp;Yufei Wang,&nbsp;Fangqi Hu,&nbsp;Xiaofeng Wang,&nbsp;Jiazi Zhang,&nbsp;Yongsheng Wang,&nbsp;Jie Chai","doi":"10.1111/febs.70102","DOIUrl":"10.1111/febs.70102","url":null,"abstract":"<p>Immunogenic cell death is a tumor cell death involving both innate and adaptive immune responses. Given the published findings that oxaliplatin causes the secretion of high mobility group box 1 (HMGB1) from cancer cells, which is necessary for the initiation of immunogenic cell death, we investigated whether oxaliplatin plays an anticancer role in gastric cancer by inducing immunogenic cell death and further explored its mechanism. We found that oxaliplatin inhibited viability and induced pyroptosis, immunogenic cell death, the production of reactive oxygen species, mitochondrial permeability transition pore (mPTP) opening, and cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) axis activation in gastric cancer cells. Suppressing mPTP opening (cyclosporine treatment), depleting mitochondrial DNA (mtDNA; ethidium bromide treatment), or STING downregulation (H151 or si-STING treatment) reversed cGAS/STING pathway activation and the increased immunogenic cell death induced by oxaliplatin in MKN-45 and AGS cells. Moreover, oxaliplatin induced immunogenic cell death via activating the cGAS/STING/TANK-binding kinase 1 (TBK1; also known as serine/threonine-protein kinase TBK1)/interferon regulatory factor 5 (IRF5) pathway. In conclusion, oxaliplatin treatment could induce immunogenic cell death and mPTP opening and activate the cGAS/STING/TBK1/IRF5 pathway in gastric cancer cells.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 14","pages":"3814-3828"},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034365","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}

{"title":"Measuring catalytic mechanism similarity - a new approach to study enzyme function and evolution.","authors":"Antonio J M Ribeiro, Ioannis G Riziotis, Neera Borkakoti, Pedro A Fernandes, Maria J Ramos, Janet M Thornton","doi":"10.1111/febs.70106","DOIUrl":"https://doi.org/10.1111/febs.70106","url":null,"abstract":"<p><p>Similarity measures for protein sequence, structure and enzyme reactions have been essential tools for translating an abundance of experimental data about enzymes into biological insights. Enzymes with similar sequence and structure, for example, can be organised into evolutionary families, and within families, reaction similarity can highlight examples of conservation or divergent evolution. When it comes to reaction mechanisms, despite their importance in explaining the catalytic power of enzymes and their evolution, no similarity measures have been developed until now. We addressed this gap by developing a method to calculate mechanism similarity based on the bond changes and charge transfers occurring at each catalytic step, where we have the ability to adjust the size of the chemical environment surrounding the atoms directly involved in these transformations. Using this newly developed method, we performed a pairwise comparison of all the mechanisms stored in the Mechanism and Catalytic Site Atlas (M-CSA) database. This analysis illustrates how mechanism similarity can be a powerful tool to navigate the known catalytic space and to discover and characterise both convergent and divergent evolutionary relationships.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000983","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}

{"title":"New insights into Sti1/Hop's cochaperone function highlight the complexity of proteostatic regulation","authors":"Gregory Lloyd Blatch,&nbsp;Adrienne Lesley Edkins","doi":"10.1111/febs.70108","DOIUrl":"10.1111/febs.70108","url":null,"abstract":"<p>Sti1/Hop is a cochaperone that regulates Hsp70 and Hsp90 chaperones. Sti1/Hop function is perceived as limited to scaffolding chaperone complexes, although recent studies suggest a broader function. Rutledge <i>et al.</i> show that while Sti1/Hop functions within chaperone complexes under basal conditions, during high stress, it operates independently to sequester soluble misfolded protein in the cytoplasm, a function typically associated with chaperones rather than cochaperones. Furthermore, the localisation and levels of Sti1/Hop are finely tuned to ensure orderly sequestration and resolution of misfolded proteins. These data support a role for Sti1/Hop as a cochaperone specialised for stressed proteostasis networks.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 14","pages":"3629-3633"},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional insights into extreme thermal stability and activity of two GH12 domains of a multidomain glycosidase from a hyperthermophilic euryarchaeon","authors":"Kseniya S. Zayulina,&nbsp;Evgenii N. Frolov,&nbsp;Christina Stracke,&nbsp;Alexandra A. Klyukina,&nbsp;Anna N. Khusnutdinova,&nbsp;Peter Stogios,&nbsp;Tatiana Skarina,&nbsp;Alexander F. Yakunin,&nbsp;Peter N. Golyshin,&nbsp;Bettina Siebers,&nbsp;Tatiana E. Shugaeva,&nbsp;Ilya V. Kublanov","doi":"10.1111/febs.70095","DOIUrl":"10.1111/febs.70095","url":null,"abstract":"<p>Bacteria and fungi are well known for efficient degradation of plant polysaccharides thanks to various enzymes involved in plant cell wall decomposition. However, little is known about the role of archaea in this process or the repertoire and features of their polysaccharide-degrading enzymes. In our previous work, we discovered an archaeal multidomain glycosidase (MDG) composed of three catalytic domains (GH5 and two GH12) and two cellulose-binding modules (CBM2). The recombinant MDG and individual GH5 catalytic domain were active against cellulose and a number of other polysaccharides at a wide range of temperatures, with optimum temperatures (<i>T</i>_opt) of 60 °C and 80 °C, respectively. The present study was focused on the characterization of two GH12 domains of the MDG. Purified recombinant TMDG_GH12-1 and TMDG_GH12-2 proteins were active as individual enzymes but exhibited distinct catalytic properties. Both enzymes were thermostable and active at extremely high temperatures: TMDG_GH12-1 was active at 40–130 °C (<i>T</i>_opt 100 °C), and its half-life (<i>t</i>_½) at 100 °C was 42 h, which makes it one of the most thermostable glycosidases known so far, whereas TMDG_GH12-2 was active at 50–100 °C (<i>T</i>_opt 90 °C) with <i>t</i>_½ at 100 °C being 30 min. Phylogenetic and structural analysis of both TMDG_GH12 proteins together with molecular docking and site-directed mutagenesis suggested that the presence of two disulfide bridges and the W → Q mutation in the active site contribute to the exceptional thermostability of TMDG_GH12-1. Further structural and mutational studies of the TMDG_GH12-1 domain will help to gain a better understanding of the molecular mechanisms of its extraordinary thermostability and substrate specificity.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":"292 14","pages":"3771-3794"},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/febs.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}