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Unlocking the biochemical secrets of longevity: balancing healthspan and lifespan 揭开长寿的生化秘密：平衡健康寿命和寿命。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-07-02 DOI: 10.1002/1873-3468.14963
Jose Viña, Consuelo Borrás
{"title":"Unlocking the biochemical secrets of longevity: balancing healthspan and lifespan","authors":"Jose Viña,&nbsp;Consuelo Borrás","doi":"10.1002/1873-3468.14963","DOIUrl":"10.1002/1873-3468.14963","url":null,"abstract":"<p>In an era of rising global life expectancies, research focuses on enhancing the quality of extended years. This review examines the link between mitochondrial function and aging, highlighting the importance of healthspan alongside lifespan. This involves significant human and economic challenges, with longer lifespans often accompanied by reduced well-being. Addressing mitochondrial decline, exploring targeted interventions, and understanding the complexities of research models are vital for advancing our knowledge in this field. Additionally, promoting physical exercise and adopting personalized supplementation strategies based on individual needs can contribute to healthy aging. The insights from this Perspective article offer a hopeful outlook for future advances in extending both lifespan and healthspan, aiming to improve the overall quality of life in aging populations.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491498","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
Poliovirus capsid protein VP3 can penetrate vascular endothelial cells 脊髓灰质炎病毒壳蛋白 VP3 可以穿透血管内皮细胞。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-07-02 DOI: 10.1002/1873-3468.14974
Taketoshi Mizutani, Aya Ishizaka
{"title":"Poliovirus capsid protein VP3 can penetrate vascular endothelial cells","authors":"Taketoshi Mizutani,&nbsp;Aya Ishizaka","doi":"10.1002/1873-3468.14974","DOIUrl":"10.1002/1873-3468.14974","url":null,"abstract":"<p>The poliovirus (PV) enters the central nervous system (CNS) <i>via</i> the bloodstream, suggesting the existence of a mechanism to cross the blood–brain barrier. Here, we report that PV capsid proteins (VP1 and VP3) can penetrate cells, with VP3 being more invasive. Two independent parts of VP3 are responsible for this function. Both peptides can penetrate human umbilical cord vascular endothelial cells, and one peptide of VP3 could also penetrate peripheral blood mononuclear cells. In an <i>in vitro</i> blood–brain barrier model using rat-derived astrocytes, pericytes, and endothelial cells, both peptides were observed to traverse from the blood side to the brain side at 6 h after administration. These results provide insights into the molecular mechanisms underlying PV invasion into the CNS.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491497","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
Host–diet–microbiota interplay in intestinal nutrition and health 肠道营养与健康中的宿主-饮食-微生物群相互作用。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-30 DOI: 10.1002/1873-3468.14966
Anastasia Ignatiou, Chrysoula Pitsouli
{"title":"Host–diet–microbiota interplay in intestinal nutrition and health","authors":"Anastasia Ignatiou,&nbsp;Chrysoula Pitsouli","doi":"10.1002/1873-3468.14966","DOIUrl":"10.1002/1873-3468.14966","url":null,"abstract":"<p>The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet–microbiota–host interactions depend on the use of genetically tractable models, such as <i>Drosophila melanogaster</i>. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the <i>Drosophila</i> model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14966","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467202","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
A modified glycosylase base editor without predictable DNA off-target effects 改良的糖基化酶碱基编辑器不会产生可预测的 DNA 脱靶效应。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-30 DOI: 10.1002/1873-3468.14970
Meng Lian, Tao Chen, Min Chen, Xiaohua Peng, Yang Yang, Xian Luo, Yue Chi, Jinling Wang, Chengcheng Tang, Xiaoqing Zhou, Kun Zhang, Chuan Qin, Liangxue Lai, Jizeng Zhou, Qingjian Zou
{"title":"A modified glycosylase base editor without predictable DNA off-target effects","authors":"Meng Lian,&nbsp;Tao Chen,&nbsp;Min Chen,&nbsp;Xiaohua Peng,&nbsp;Yang Yang,&nbsp;Xian Luo,&nbsp;Yue Chi,&nbsp;Jinling Wang,&nbsp;Chengcheng Tang,&nbsp;Xiaoqing Zhou,&nbsp;Kun Zhang,&nbsp;Chuan Qin,&nbsp;Liangxue Lai,&nbsp;Jizeng Zhou,&nbsp;Qingjian Zou","doi":"10.1002/1873-3468.14970","DOIUrl":"10.1002/1873-3468.14970","url":null,"abstract":"<p>Glycosylase base editor (GBE) can induce C-to-G transversion in mammalian cells, showing great promise for the treatment of human genetic disorders. However, the limited efficiency of transversion and the possibility of off-target effects caused by Cas9 restrict its potential clinical applications. In our recent study, we have successfully developed TaC9-CBE and TaC9-ABE by separating nCas9 and deaminase, which eliminates the Cas9-dependent DNA off-target effects without compromising editing efficiency. We developed a novel GBE called TaC9-GBE<sup>YE1</sup>, which utilizes the deaminase and UNG-nCas9 guided by TALE and sgRNA, respectively. TaC9-GBE<sup>YE1</sup> showed comparable levels of on-target editing efficiency to traditional GBE at 19 target sites, without any off-target effects caused by Cas9 or TALE. The TaC9-GBE<sup>YE1</sup> is a safe tool for gene therapy.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467200","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
Photosystems and photoreceptors in cyanobacterial phototaxis and photophobotaxis 蓝藻趋光性和亲光性中的光系统和光感受器
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-30 DOI: 10.1002/1873-3468.14968
Tilman Lamparter
{"title":"Photosystems and photoreceptors in cyanobacterial phototaxis and photophobotaxis","authors":"Tilman Lamparter","doi":"10.1002/1873-3468.14968","DOIUrl":"10.1002/1873-3468.14968","url":null,"abstract":"<p>Cyanobacteria move by gliding motility on surfaces toward the light or away from it. It is as yet unclear how the light direction is sensed on the molecular level. Diverse photoreceptor knockout mutants have a stronger response toward the light than the wild type. Either the light direction is sensed by multiple photoreceptors or by photosystems. In a study on photophobotaxis of the filamentous cyanobacterium <i>Phormidium lacuna</i>, broad spectral sensitivity, inhibition by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), and a highly sensitive response speaks for photosystems as light direction sensors. Here, it is discussed whether the photosystem theory could hold for phototaxis of other cyanobacteria.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467203","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
Dissecting the structural and functional consequences of the evolutionary proline–glycine deletion in the wing 1 region of the forkhead domain of human FoxP1 剖析人类 FoxP1 叉头结构域翼 1 区脯氨酸-甘氨酸缺失的结构和功能后果。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-30 DOI: 10.1002/1873-3468.14972
Stephanie Tamarín, Pablo Galaz-Davison, César A. Ramírez-Sarmiento, Jorge Babul, Exequiel Medina
{"title":"Dissecting the structural and functional consequences of the evolutionary proline–glycine deletion in the wing 1 region of the forkhead domain of human FoxP1","authors":"Stephanie Tamarín,&nbsp;Pablo Galaz-Davison,&nbsp;César A. Ramírez-Sarmiento,&nbsp;Jorge Babul,&nbsp;Exequiel Medina","doi":"10.1002/1873-3468.14972","DOIUrl":"10.1002/1873-3468.14972","url":null,"abstract":"<p>The human FoxP transcription factors dimerize <i>via</i> three-dimensional domain swapping, a unique feature among the human Fox family, as result of evolutionary sequence adaptations in the forkhead domain. This is the case for the conserved glycine and proline residues in the wing 1 region, which are absent in FoxP proteins but present in most of the Fox family. In this work, we engineered both glycine (G) and proline–glycine (PG) insertion mutants to evaluate the deletion events in FoxP proteins in their dimerization, stability, flexibility, and DNA-binding ability. We show that the PG insertion only increases protein stability, whereas the single glycine insertion decreases the association rate and protein stability and promotes affinity to the DNA ligand.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467201","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
Correction to: Selection of bifunctional RNAs with specificity for arginine and lipid membranes 更正：选择对精氨酸和脂膜具有特异性的双功能 RNA。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-26 DOI: 10.1002/1873-3468.14965
{"title":"Correction to: Selection of bifunctional RNAs with specificity for arginine and lipid membranes","authors":"","doi":"10.1002/1873-3468.14965","DOIUrl":"10.1002/1873-3468.14965","url":null,"abstract":"<p>Janas T, Sapoń K and Janas T (2024) <i>FEBS Lett</i> <b>598</b>, 1061–1079. https://doi.org/10.1002/1873-3468.14880</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456136","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
Effects of interrupting residues on DNA dumbbell structures formed by CCTG tetranucleotide repeats associated with myotonic dystrophy type 2 中断残基对与肌营养不良症 2 型有关的 CCTG 四核苷酸重复序列所形成的 DNA 哑铃结构的影响。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-25 DOI: 10.1002/1873-3468.14952
Yingquan Yang, Yang Wang, Zhenzhen Yan, Zhigang Li, Pei Guo
{"title":"Effects of interrupting residues on DNA dumbbell structures formed by CCTG tetranucleotide repeats associated with myotonic dystrophy type 2","authors":"Yingquan Yang,&nbsp;Yang Wang,&nbsp;Zhenzhen Yan,&nbsp;Zhigang Li,&nbsp;Pei Guo","doi":"10.1002/1873-3468.14952","DOIUrl":"10.1002/1873-3468.14952","url":null,"abstract":"<p>Myotonic dystrophy type 2 (DM2) is a neurogenerative disease caused by caprylic/capric triglyceride (CCTG) tetranucleotide repeat expansions in intron 1 of the cellular nucleic acid-binding protein (<i>CNBP</i>) gene. Non-B DNA structures formed by CCTG repeats can promote genetic instability, whereas interrupting motifs of NCTG (N = A/T/G) within CCTG repeats help to maintain genomic stability. However, whether the interrupting motifs can affect DNA structures of CCTG repeats remains unclear. Here, we report that four CCTG repeats with an interrupting 3′-A/T/G residue formed dumbbell structures, whereas a non-interrupting 3′-C residue resulted in a multi-loop structure exhibiting conformational dynamics that may contribute to a higher tendency of escaping from DNA mismatch repair and causing repeat expansions. The results provide new structural insights into the genetic instability of CCTG repeats in DM2.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456137","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
Mitochondrial respiratory complex I can be inhibited via bypassing the ubiquinone-accessing tunnel 线粒体呼吸复合体 I 可通过绕过泛醌通道而受到抑制。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-25 DOI: 10.1002/1873-3468.14967
Ryohei Otani, Takahiro Masuya, Hideto Miyoshi, Masatoshi Murai
{"title":"Mitochondrial respiratory complex I can be inhibited via bypassing the ubiquinone-accessing tunnel","authors":"Ryohei Otani,&nbsp;Takahiro Masuya,&nbsp;Hideto Miyoshi,&nbsp;Masatoshi Murai","doi":"10.1002/1873-3468.14967","DOIUrl":"10.1002/1873-3468.14967","url":null,"abstract":"<p>Mitochondrial NADH–ubiquinone oxidoreductase (complex I) couples electron transfer from NADH to ubiquinone with proton translocation in its membrane part. Structural studies have identified a long (~ 30 Å), narrow, tunnel-like cavity within the enzyme, through which ubiquinone may access a deep reaction site. Although various inhibitors are considered to block the ubiquinone reduction by occupying the tunnel's interior, this view is still debatable. We synthesized a phosphatidylcholine-quinazoline hybrid compound (PC-Qz1), in which a quinazoline-type toxophore was attached to the <i>sn</i>-2 acyl chain to prevent it from entering the tunnel. However, PC-Qz1 inhibited complex I and suppressed photoaffinity labeling by another quinazoline derivative, [<sup>125</sup>I]AzQ. This study provides further experimental evidence that is difficult to reconcile with the canonical ubiquinone-accessing tunnel model.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.14967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456138","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
SIRT5 mutants reveal the role of conserved asparagine and glutamine residues in the NAD+-binding pocket SIRT5 突变体揭示了 NAD+ 结合袋中保守的天冬酰胺和谷氨酰胺残基的作用
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2024-06-20 DOI: 10.1002/1873-3468.14961
Takeshi Yokoyama, Yuki Takayama, Mineyuki Mizuguchi, Yuko Nabeshima, Katsuhiro Kusaka
{"title":"SIRT5 mutants reveal the role of conserved asparagine and glutamine residues in the NAD+-binding pocket","authors":"Takeshi Yokoyama,&nbsp;Yuki Takayama,&nbsp;Mineyuki Mizuguchi,&nbsp;Yuko Nabeshima,&nbsp;Katsuhiro Kusaka","doi":"10.1002/1873-3468.14961","DOIUrl":"10.1002/1873-3468.14961","url":null,"abstract":"<p>SIRT5, one of the mammalian sirtuins, specifically recognizes succinyl-lysine residues on proteins and catalyzes the desuccinylation reaction. In this study, we characterized SIRT5 mutants with hydrophobic amino acid substitutions at Q140 and N141, in addition to the catalytic residue H158, known as an active site residue, by the Michaelis–Menten analysis and X-ray crystallography. Kinetic analysis showed that the catalytic efficiency (<i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub>) of the Q140L and N141V mutants decreased to 0.02 times and 0.0038 times that of the wild-type SIRT5, respectively, with the activity of the N141V mutant becoming comparable to that of the H158M mutant. Our findings indicate that N141 contributes significantly to the desuccinylation reaction.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141523677","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
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