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Structural diversity of pyruvate dehydrogenase complexes. 丙酮酸脱氢酶复合物的结构多样性。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-13 DOI: 10.1002/1873-3468.70140
Sarah N Bothe, Rafal Zdanowicz
{"title":"Structural diversity of pyruvate dehydrogenase complexes.","authors":"Sarah N Bothe, Rafal Zdanowicz","doi":"10.1002/1873-3468.70140","DOIUrl":"https://doi.org/10.1002/1873-3468.70140","url":null,"abstract":"<p><p>The pyruvate dehydrogenase complex (PDHc) is a crucial metabolic enzyme complex found in all aerobic organisms. It catalyzes the conversion of pyruvate, the product of glycolysis, into acetyl-CoA, a key substrate for the citric acid cycle and fatty acid synthesis. This multienzyme complex uses multiple cosubstrates and tethered reaction intermediates to efficiently channel substrates through its catalytic steps. With a total size of 5-12 MDa, PDHc is among the largest biomolecular assemblies. It consists of three enzymatic components acting sequentially: E1 (pyruvate dehydrogenase), E2 (dihydrolipoamide acetyltransferase), and E3 (dihydrolipoamide dehydrogenase). In eukaryotes, an additional E3-binding protein (E3BP) recruits E3 to the complex. E2 (and E3BP) subunits form the structural core, typically exhibiting octahedral or icosahedral symmetry, while E1 and E3 bind to the core as peripheral subunits. Advances in structural biology, particularly cryo-EM, X-ray crystallography, and nuclear magnetic resonance (NMR), have provided valuable insights into PDHc organization, assembly principles, and species-specific variation. Here, we review diverse PDHc architectures across phylogenetic groups. Understanding these structural and functional adaptations is essential for fully deciphering PDHc regulation and its role in metabolism.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845059","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}
引用次数: 0
Development of visible light-sensitive human neuropsin (OPN5) via single amino acid substitution 通过单氨基酸取代制备可见光敏人神经素(OPN5)。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-13 DOI: 10.1002/1873-3468.70130
Yusuke Sakai, Richard J. McDowell, Robert J. Lucas
{"title":"Development of visible light-sensitive human neuropsin (OPN5) via single amino acid substitution","authors":"Yusuke Sakai,&nbsp;Richard J. McDowell,&nbsp;Robert J. Lucas","doi":"10.1002/1873-3468.70130","DOIUrl":"10.1002/1873-3468.70130","url":null,"abstract":"<p>Neuropsin (Opn5), a UV-sensitive ‘non-visual’ opsin, has the potential to be used as optogenetic tools applicable to tissues outside of the eye because of its broad expression. However, its sensitivity to poorly tissue-penetrating UV light poses challenges for its application. In this study, we focused on human OPN5 (hOPN5) to identify amino acid(s) responsible for the UV sensitivity. Sequence alignment across UV-sensitive Opn5s identified a conserved lysine residue (Lys91) at a position implicated in spectral tuning in invertebrate opsins. Substitution of this residue with neutral or acidic amino acids caused substantial shifts in spectral sensitivity towards visible wavelengths. Our findings identify Lys91 as a key spectral tuning site in hOPN5 and provide visible-light-sensitive versions as a candidate for optogenetic applications.</p><p>\u0000 \u0000 </p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 18","pages":"2612-2619"},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Autophagy in the regulation of cancer dormancy 自噬在调节癌症休眠中的作用。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-13 DOI: 10.1002/1873-3468.70139
Damla Gunes, Alara Ustal, Yusuf Emre Ertem, Yunus Akkoc, Devrim Gozuacik
{"title":"Autophagy in the regulation of cancer dormancy","authors":"Damla Gunes,&nbsp;Alara Ustal,&nbsp;Yusuf Emre Ertem,&nbsp;Yunus Akkoc,&nbsp;Devrim Gozuacik","doi":"10.1002/1873-3468.70139","DOIUrl":"10.1002/1873-3468.70139","url":null,"abstract":"<p>Relapse and metastasis continue to be major factors in cancer patient morbidity and death. Cancer dormancy is one of the reasons why cancer recurs after months or years of treatment. With the ability to reactivate, dormant tumors are transitioning into a growth latency stage that shields them from immune surveillance and traditional chemotherapy medications. Over the past decade, research efforts have concentrated on understanding processes governing the dormant state better. The ultimate goal of these efforts is to improve cancer diagnosis, treatment of metastatic illness, and prevention of relapse. Cancer tolerance to stress may depend on autophagy, a cellular stress and recycling system that promotes cancer growth and survival. Recent studies indicated that autophagy may help cancer cells to survive in primary and metastatic environments, to withstand treatment, to develop a dormant state, and to transition from the dormancy to a proliferative state. In this Review, we will discuss the autophagy–dormancy connection in primary and metastatic cancer.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 16","pages":"2272-2300"},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring lipid diversity and minimalism to define membrane requirements for synthetic cells. 探索脂质多样性和极简主义来定义合成细胞的膜要求。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-11 DOI: 10.1002/1873-3468.70131
Sergiy Gan, Victoria Scarpelli, Marten Exterkate
{"title":"Exploring lipid diversity and minimalism to define membrane requirements for synthetic cells.","authors":"Sergiy Gan, Victoria Scarpelli, Marten Exterkate","doi":"10.1002/1873-3468.70131","DOIUrl":"https://doi.org/10.1002/1873-3468.70131","url":null,"abstract":"<p><p>The creation of minimal synthetic cells that mimic the essential functions of biological cells is a long-term goal in synthetic biology. Achieving this objective not only advances our understanding of the origin of life, but also unlocks the way for applications in industry, medicine, etc. A key characteristic of life is self-reproduction, which includes growth and division of the cell and its membrane. This boundary layer is formed by a lipid matrix in which proteins are anchored. The complexity of natural lipid membranes is a major challenge for the construction of a minimal system, as it directly influences membrane shape and protein function. Although simple synthetic compartmentalization systems can consist of a single lipid species, there is substantial uncertainty regarding the complexity of the lipidome required to sustain the essential functions of a self-reproducing cell. This Review highlights the contrast between bottom-up and top-down approaches toward synthetic cell construction, emphasizing the critical interplay between membrane proteins and their surrounding lipid environment. We explore the complexity and compatibility of membrane systems and discuss minimal lipidome requirements for synthetic cellular systems. Impact statement Synthetic cell research will help us to truly understand the basic principles of cellular life, in which lipid membranes are crucial. Ultimately, synthetic cells should lead to engineered specialized entities that can be applied in various fields, including medicine, bio-technology, and environmental science.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816110","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}
引用次数: 0
D2-type dopamine receptors are required for LPS-induced acute hematopoiesis. 脂多糖诱导的急性造血需要d2型多巴胺受体。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-11 DOI: 10.1002/1873-3468.70143
Jia-Xin Yang, Yu-Yan Li, Zhao-Hua Deng, Tian-Jing Li, Ke Bai, Yan-Mei Yu, Jinjin Ma, Qi Chen, Yang Liu
{"title":"D2-type dopamine receptors are required for LPS-induced acute hematopoiesis.","authors":"Jia-Xin Yang, Yu-Yan Li, Zhao-Hua Deng, Tian-Jing Li, Ke Bai, Yan-Mei Yu, Jinjin Ma, Qi Chen, Yang Liu","doi":"10.1002/1873-3468.70143","DOIUrl":"https://doi.org/10.1002/1873-3468.70143","url":null,"abstract":"<p><p>Hematopoietic stem and progenitor cells (HSPCs) rapidly proliferate during infection and stress to replenish immune cells, which is essential for host defense. Dopamine, released by bone marrow (BM) nerves, regulates HSPCs via D2-type dopamine receptors. However, their role in emergency hematopoiesis across organs is unclear. We show that D2-type receptors are crucial for hematopoiesis in BM, spleen, lymph nodes, and thymus. Genetic deletion of D2-type receptors in hematopoietic cells (DKO<sup>∆HC</sup>) impairs HSPC proliferation and reduces blood cell production under lipopolysaccharide (LPS) stimulation, particularly in BM and spleen. Limited defects are observed in lymphoid organs. Mechanistically, D2-type signaling modulates the LPS-activated TAK1-ERK pathway via Lck. The inhibition of Lck mimics decreased ERK phosphorylation seen in DKO<sup>∆HC</sup> HSPCs, revealing the important role of dopamine signals in LPS-TLR4-mediated responses.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948176","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}
引用次数: 0
Microbial exopolysaccharide production by polyextremophiles in the adaptation to multiple extremes. 多极端微生物在适应多种极端条件时产生的胞外多糖。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-08 DOI: 10.1002/1873-3468.70138
Tracey M Gloster, Ebru Toksoy Öner
{"title":"Microbial exopolysaccharide production by polyextremophiles in the adaptation to multiple extremes.","authors":"Tracey M Gloster, Ebru Toksoy Öner","doi":"10.1002/1873-3468.70138","DOIUrl":"https://doi.org/10.1002/1873-3468.70138","url":null,"abstract":"<p><p>Over the past few decades, research on polyextremophiles has revealed a diverse range of organisms adapted to multiple extreme conditions, such as combinations of high and low temperatures, acidity, pressure, salinity, and radiation. Under multiple extremes, a key survival mechanism is the production of exopolysaccharides (EPSs) via cell wall-associated or extracellular glycosyltransferases (GTs). EPSs not only protect cells against environmental extremes, desiccation, phage attacks, phagocytosis, and antibiotics; they also play important roles in inter- and intra-microbial interactions, quorum sensing, virulence, energy storage, and biofilm formation. Despite extensive studies on EPSs from extremophiles, knowledge on EPS production in polyextremophiles remains limited, particularly for psychrophiles, halophiles, and piezophiles. This review focuses on the adaptive strategies of polyextremophiles under multiple stress conditions, emphasizing the functional significance of EPS production. By providing an integrated perspective on polyextremophiles and their survival mechanisms, this work highlights the critical role of EPSs in their adaptation to extreme habitats and their potential biotechnological applications.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803944","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}
引用次数: 0
Regulation of mRNA metabolism in immune cells 免疫细胞mRNA代谢的调控。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-08 DOI: 10.1002/1873-3468.70132
Manendra Singh Negi, Blagoje Soskic, Ivano Legnini
{"title":"Regulation of mRNA metabolism in immune cells","authors":"Manendra Singh Negi,&nbsp;Blagoje Soskic,&nbsp;Ivano Legnini","doi":"10.1002/1873-3468.70132","DOIUrl":"10.1002/1873-3468.70132","url":null,"abstract":"<p>Rapid activation of immune cells is critical for host defence. While transcriptional regulation is essential for initiating the immune response, emerging evidence highlights the role of post-transcriptional mechanisms in controlling the speed and intensity of the immune reaction. Splicing, polyadenylation, translation and decay are all regulated to fine-tune the expression of genes crucial for immune cell activation and differentiation. Therefore, it is not surprising that impaired mRNA regulation results in susceptibility to infection, inflammation or immune deficiency. An in-depth understanding of these processes is critical for developing novel therapies for immune diseases. This Review provides an integrative view of how mRNA splicing, polyadenylation and decay control immune cell activation and effector function.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 18","pages":"2571-2581"},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
C-mannosylation promotes ADAMTS1 activation and secretion in human testicular germ cell tumor NEC8 cells. c -甘露糖基化促进人睾丸生殖细胞瘤NEC8细胞ADAMTS1的激活和分泌。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-06 DOI: 10.1002/1873-3468.70133
Takato Kobayashi, Takehiro Suzuki, Ryota Kawahara, Natsumi Harai, Naoshi Dohmae, Siro Simizu
{"title":"C-mannosylation promotes ADAMTS1 activation and secretion in human testicular germ cell tumor NEC8 cells.","authors":"Takato Kobayashi, Takehiro Suzuki, Ryota Kawahara, Natsumi Harai, Naoshi Dohmae, Siro Simizu","doi":"10.1002/1873-3468.70133","DOIUrl":"https://doi.org/10.1002/1873-3468.70133","url":null,"abstract":"<p><p>C-mannosylation is a protein glycosylation that regulates the functions of target proteins. Although it has been reported that a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), an important spermatogenesis factor, is C-mannosylated, the roles of C-mannosylation in ADAMTS1 in testicular cells are still unclear. In this study, we found that ADAMTS1 is C-mannosylated at Trp<sup>562</sup> and Trp<sup>565</sup> in testis germ NEC8 cells. To determine the roles of C-mannosylation in ADAMTS1, we established cells expressing a C-mannosylation-defective ADAMTS1, in which C-mannosylated tryptophan residues were replaced with phenylalanine residues (ADAMTS1/2WF). Processing and secretion of ADAMTS1/2WF were both inhibited compared to those of wild-type. Moreover, wild-type ADAMTS1 degraded aggrecan, whereas ADAMTS1/2WF could not. These results indicate the impact of C-mannosylation on ADAMTS1 function.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948154","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}
引用次数: 0
Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy. 麦角硫因补充改善幼犬表型和小鼠脊髓性肌萎缩模型的存活率。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-06 DOI: 10.1002/1873-3468.70136
Francesca Cadile, Daniela Ratto, Giorgia Rastelli, Ottavia Eleonora Ferraro, Caterina Temporini, Sunil Kumar, Simona Boncompagni, Paola Rossi, Monica Canepari
{"title":"Ergothioneine supplementation improves pup phenotype and survival in a murine model of spinal muscular atrophy.","authors":"Francesca Cadile, Daniela Ratto, Giorgia Rastelli, Ottavia Eleonora Ferraro, Caterina Temporini, Sunil Kumar, Simona Boncompagni, Paola Rossi, Monica Canepari","doi":"10.1002/1873-3468.70136","DOIUrl":"https://doi.org/10.1002/1873-3468.70136","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons. The conventional therapy does not always lead to a full restoration of the clinical symptoms, partially due to the need for early treatment. Accumulating evidence describes the crucial role of mitochondrial dysfunction and oxidative stress in skeletal muscle of SMA patients. We aimed to investigate the effects of prenatal supplementation with the antioxidant molecule ergothioneine (ERGO) on an SMNΔ7 mouse model of SMA containing a knockout of survival motor neuron protein (SMN1) and two transgenes, one with a single normal copy of human SMN2 and the second with a human SMN2 promoter and a human SMN2 cDNA lacking exon 7. ERGO had a significant positive effect on the survival and locomotor abilities of SMA pups. In isolated diaphragm muscle, ERGO was found to stimulate mitophagy. The results of the current study highlight the need for further research into ERGO as an adjuvant therapy for SMA. Impact statement Our finding that ergothioneine supplementation improves survival in a murine model of spinal muscular atrophy may aid research into a novel potential adjuvant to alleviate the symptoms of this serious neuromuscular disease in humans.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793862","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}
引用次数: 0
Building the lab together – from day one 一起建立实验室,从第一天开始。
IF 3 4区 生物学
FEBS Letters Pub Date : 2025-08-06 DOI: 10.1002/1873-3468.70137
Hans-Georg Sprenger, Julia Hansen
{"title":"Building the lab together – from day one","authors":"Hans-Georg Sprenger,&nbsp;Julia Hansen","doi":"10.1002/1873-3468.70137","DOIUrl":"10.1002/1873-3468.70137","url":null,"abstract":"<p>What are the most challenging and rewarding aspects of starting a new laboratory? In this article, we interview Hans-Georg-Sprenger, who recently started his own research group “Molecular Metabolism &amp; Energy Homeostasis” at the Max Planck Institute for Biology of Ageing in Cologne. From the first PhD student to the first experiments, and from early discoveries and troubleshooting to the first bachelor's thesis defense, the people in the laboratory are central. For Hans-Georg Sprenger, helping others build their skills and independence is what makes mentoring so fulfilling.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 17","pages":"2417-2419"},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://febs.onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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