FEBS LettersPub Date : 2025-10-10DOI: 10.1002/1873-3468.70181
Dong-Woo Shin, Tingting Chen, James A Letts
{"title":"Mapping the evolution of mitochondrial complex I through structural variation.","authors":"Dong-Woo Shin, Tingting Chen, James A Letts","doi":"10.1002/1873-3468.70181","DOIUrl":"https://doi.org/10.1002/1873-3468.70181","url":null,"abstract":"<p><p>Respiratory complex I (CI) is a multi-subunit membrane protein complex important for the production of ATP via the oxidative phosphorylation pathway. The structure of CI is roughly conserved across species and is composed of subunits that are either embedded in the membrane or are exposed to the aqueous environment that together form an overall L-shaped 'boot'. The conserved core of CI is generally composed of 14 subunits. Across species, various less conserved 'supernumerary' or 'accessory' subunits have been added. Accessory subunits vary in number across species and can include proteins that are unique to specific lineages. Additionally, there are structural variations in the core subunits between clades. In this Review, we compare seven representative CI structures from divergent eukaryotic lineages to identify what aspects of the CI core subunits are susceptible to variation and classify eukaryotic accessory subunits into those conserved from the last eukaryotic common ancestor (LECA) or those that are lineage specific. Impact statement Understanding the biodiversity and evolution of mitochondrial complex I will reveal patterns that may reflect metabolic niche and can be used to constrain quantitative models of molecular evolution.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-10-10DOI: 10.1002/1873-3468.70183
Margit Aschenbrenner, Tuija Ekegren, Françoise Steinbach, Julia Hansen
{"title":"Marfan Europe Network: Together we can!","authors":"Margit Aschenbrenner, Tuija Ekegren, Françoise Steinbach, Julia Hansen","doi":"10.1002/1873-3468.70183","DOIUrl":"https://doi.org/10.1002/1873-3468.70183","url":null,"abstract":"<p><p>First described in the 19th century, Marfan syndrome is a rare hereditable genetic disease, mainly caused by mutations in FBN1 leading to connective tissue defects. While the patient phenotype is highly variable, many affected present with tall stature, long and flexible limbs and joints, eye disorders, and life-threatening aortic enlargements. Modern medical treatments can alleviate these symptoms, but it is important for people living with connective tissue disorders to learn about their situation and connect with others facing the same challenges. The Marfan Europe Network (M.E.N.) is an umbrella organization of 14 national Marfan patient organizations, integrating efforts to inform the public and improve the lives of those affected. Here, we interview Tuija Ekegren, Françoise Steinbach, and Margit Aschenbrenner from the Board of Directors of the M.E.N.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-10-09DOI: 10.1002/1873-3468.70178
Laura Norton
{"title":"We need more women in STEM.","authors":"Laura Norton","doi":"10.1002/1873-3468.70178","DOIUrl":"https://doi.org/10.1002/1873-3468.70178","url":null,"abstract":"<p><p>In the UK, women represent just 26.7% of the Science, Technology, Engineering, and Mathematics (STEM) workforce, despite making up 47.5% of the overall working population. Currently, UK businesses lose around £1.5 billion per year due to STEM skill shortages. This leads to slower adoption of new technologies, reduced productivity and increased pressure on existing staff. With the UK's Industrial Strategy recently setting out an ambition to be a global leader in science and deep tech, and a focus on strengthening the European Research Area (ERA) to boost its global competitiveness through research and innovation, it is very clear that we need change. The demand for STEM workers continues to grow, and the need for diversity and creativity is imperative.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-10-01DOI: 10.1002/1873-3468.70175
Hanna Redeker, Swantje Kebel, Lea Völkening, Anna Vatselia, Louisa Weinhold, Girmay Asgedom, Axel Schambach, Detlev Schindler, Thilo Dörk, Kristine Bousset
{"title":"RAD50 missense variants differentially affect the DNA damage response and mitotic progression.","authors":"Hanna Redeker, Swantje Kebel, Lea Völkening, Anna Vatselia, Louisa Weinhold, Girmay Asgedom, Axel Schambach, Detlev Schindler, Thilo Dörk, Kristine Bousset","doi":"10.1002/1873-3468.70175","DOIUrl":"https://doi.org/10.1002/1873-3468.70175","url":null,"abstract":"<p><p>RAD50 is the central protein of the MRN complex and crucial in DNA double-strand break repair. RAD50 deficiency causes a genomic instability disorder characterized by microcephaly and stunted growth. Using lentiviral constructs, we investigated whether cancer-related RAD50 missense variants can complement the delayed damage response after exposure to the chemotherapeutic agent epirubicin and/or mitotic progression in RAD50-deficient fibroblasts. Eight missense variants, all capable of forming an MRN complex, supported the DNA damage response and mitotic features to different extents, indicating these functions are separable. Three variants showed both an impaired epirubicin response and slowed cell division in the likely pathogenic range. Assessing RAD50 missense variants with distinct functional readouts may help to further elucidate their differential roles in immunodeficiency and cancer and could improve therapeutic strategies. Impact statement RAD50 has a strong impact on DNA repair and cancer therapy. Here, we analyse RAD50 missense variants at four functional levels. Some variants showed an impaired epirubicin response and mitotic progression in the pathological range, while for others these endpoints were separable. Functional heterogeneity of RAD50 variants could contribute to clinical variability.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-09-30DOI: 10.1002/1873-3468.70141
Alessia Santambrogio, Sofia Lövestam, Michael A Metrick, Thomas Löhr, Peifeng Xu, Nicholas C T Gallagher, Bernardino Ghetti, Byron Caughey, Sjors H W Scheres, Michele Vendruscolo
{"title":"Serial amplification of tau filaments using Alzheimer's brain homogenates and C322A or C322S recombinant tau.","authors":"Alessia Santambrogio, Sofia Lövestam, Michael A Metrick, Thomas Löhr, Peifeng Xu, Nicholas C T Gallagher, Bernardino Ghetti, Byron Caughey, Sjors H W Scheres, Michele Vendruscolo","doi":"10.1002/1873-3468.70141","DOIUrl":"https://doi.org/10.1002/1873-3468.70141","url":null,"abstract":"<p><p>The assembly of tau into amyloid filaments is a hallmark of Alzheimer's disease (AD) and other tauopathies. Cryo-EM revealed the existence of disease-specific tau folds, which are challenging to replicate in vitro. We studied three full-length recombinant 0N3R tau forms (the wild-type and the C322A and C322S variants) using an RT-QuIC assay with brain homogenate seeding. C322A tau formed filaments resembling AD paired helical filaments (PHFs) but with a more open C-shaped core. C322S tau yielded structurally distinct filaments with an ordered C-terminal region. Both mutants seeded further aggregation, whereas the wild-type showed poor reproducibility and mainly unfolded aggregates. These results highlight the importance of optimised conditions to produce disease-relevant tau filaments and aid the development of targeted therapies. Impact statement We investigated the seeded assembly of 0N3R tau and its two mutational variants C322A and C322S, using Alzheimer's disease brain homogenates in a real-time quaking-induced conversion (RT-QuIC) assay. The C322A variant formed filaments partially resembling the AD PHF structure, showing the importance of optimised conditions to produce disease-relevant tau filaments.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-09-29DOI: 10.1002/1873-3468.70174
Pramit Bhattacharjee, Atin K Mandal
{"title":"Hsp104-Hsp70-Hsp110 chaperones disintegrate kinase aggregates formed upon stress in Saccharomyces cerevisiae.","authors":"Pramit Bhattacharjee, Atin K Mandal","doi":"10.1002/1873-3468.70174","DOIUrl":"https://doi.org/10.1002/1873-3468.70174","url":null,"abstract":"<p><p>The cellular protein quality control (PQC) machinery maintains proteostasis. However, knowledge of PQC machinery-mediated handling of stress-induced misfolded proteins is still insufficient. We used the yeast kinase Ste11 to observe its fate upon heat stress or Hsp90 inhibition. We observed that while mild heat stress (37 °C) primarily resulted in proteasomal degradation of Ste11, severe heat stress (42 °C) resulted predominantly in aggregation. Ste11 aggregates sequestered with Hsp42 upon heat stress or Hsp90 inhibition. These aggregates associate with Hsp70 and Hsp104, the yeast disaggregase machinery. Notably, Ste11 aggregates disappear upon recovery from stress. This phenomenon is impaired in the absence of Hsp104 or Sse1, a co-chaperone recruited to the aggregates by Hsp70, suggesting the involvement of Hsp104, Hsp70 and Sse1 in aggregate mobilisation.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-09-25DOI: 10.1002/1873-3468.70173
Roman Kouřil
{"title":"Revealing the structure of land plant photosystem II: the journey from negative-stain EM to cryo-EM.","authors":"Roman Kouřil","doi":"10.1002/1873-3468.70173","DOIUrl":"https://doi.org/10.1002/1873-3468.70173","url":null,"abstract":"<p><p>Photosystem II (PSII) is a multi-subunit pigment-protein complex in plant chloroplasts that drives water oxidation and oxygen evolution in photosynthesis. In land plants, PSII forms dimeric core complexes associated with multiple light-harvesting complex II (LHCII) antenna proteins (LHCB1-6), assembling into large PSII-LHCII supercomplexes within thylakoid membranes. Over the past few decades, our understanding of PSII structure has advanced dramatically, evolving from low-resolution electron microscopy (EM) data to near-atomic models. This review highlights key milestones in PSII structural research, focusing on how progressive advances in EM from early negative-stain imaging to high-resolution single-particle cryo-EM, have revealed the organization of PSII supercomplexes in various plant species, ranging from angiosperms (e.g., Arabidopsis thaliana, spinach, pea) to gymnosperms (e.g., Norway spruce). These developments have led to the most detailed structural models of plant PSII to date. Future work will aim not only to determine PSII structures from a broader range of organisms, but also to explore the organization and dynamics of larger assemblies such as PSII megacomplexes and PSII-partner complexes, both in isolation and in situ within the thylakoid membrane.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-09-19DOI: 10.1002/1873-3468.70172
Francesca Noventa, Mauro Salvi
{"title":"Protein kinase FAM20C-when subcellular localization matters.","authors":"Francesca Noventa, Mauro Salvi","doi":"10.1002/1873-3468.70172","DOIUrl":"https://doi.org/10.1002/1873-3468.70172","url":null,"abstract":"<p><p>Protein kinases achieve signaling specificity through consensus sequence recognition and subcellular localization. Although motif analysis can predict potential substrates, this method is insufficient if the spatial context in which the kinase operates is not considered. FAM20C, an acidophilic kinase that is primarily localized to the Golgi lumen, is an example of this. Its preference for the SXE motif informs substrate selection, but only within compartments accessible to the enzyme. Assigning substrates based solely on motif presence can be misleading and requires integrative experimental strategies to determine whether specific conditions enable kinase-substrate proximity.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-09-19DOI: 10.1002/1873-3468.70171
Robbie Loewith, Lucas Tafur
{"title":"TOR signaling on membranes.","authors":"Robbie Loewith, Lucas Tafur","doi":"10.1002/1873-3468.70171","DOIUrl":"https://doi.org/10.1002/1873-3468.70171","url":null,"abstract":"<p><p>The Target of Rapamycin (TOR) is a highly conserved protein kinase that regulates cell growth and metabolism through two distinct complexes, TORC1 and TORC2. Each complex regulates different downstream targets; however, both are activated and regulated on lipid membranes. In this Perspective, we will revise the structural biology of TOR complexes and the molecular mechanisms governing their regulation, highlighting the importance of lipid membranes for their function.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-09-18DOI: 10.1002/1873-3468.70168
{"title":"RETRACTION: Evidence That Low Doses of Taxol Enhance the Functional Transactivatory Properties of p53 on p21 Waf Promoter in MCF-7 Breast Cancer Cells.","authors":"","doi":"10.1002/1873-3468.70168","DOIUrl":"https://doi.org/10.1002/1873-3468.70168","url":null,"abstract":"<p><strong>Retraction: </strong>M. L. Panno , F. Giordano , F. Mastroianni , C. Morelli , E. Brunelli , M. G. Palma , M. Pellegrino , S. Aquila , A. Miglietta , L. Mauro , D. Bonofiglio , and S. Andò , \"Evidence That Low Doses of Taxol Enhance the Functional Transactivatory Properties of p53 on p21 Waf Promoter in MCF-7 Breast Cancer Cells,\" FEBS Letters 580, no. 9 (2006): 2371-2380, https://doi.org/10.1016/j.febslet.2006.03.055. The above article, published online on 29 March 2006 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Michael Brunner; FEBS Press; and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation prompted by concerns raised by a third party. The investigation identified inappropriate duplications of image sections in Figures 4, 5, and 10. The authors' explanation was found to be insufficient to resolve these concerns, and due to the time elapsed since the original publication, the raw data could no longer be retrieved. However, the extent and nature of the inconsistencies identified in the published figures raised significant concerns regarding the data. As a result, the editors no longer have confidence in the integrity of the presented data and consider the study's conclusions to be compromised. The authors do not agree with this retraction.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}