Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.06.003
Yashu Zhang , Khair Bux , Fedaa Attana , Dengguo Wei , Shozeb Haider , Gary N. Parkinson
To rationalise the binding of specific ligands to RNA-quadruplex we investigated several naphthalene diimide ligands that interact with the non-coding region of Pseudorabies virus (PRV). Herein we report on the x-ray structure of the naphthalene diimide ND11 with an RNA G-quadruplex putative forming sequence from rPRV. Consistent with previously observed rPRV sequence it assembles into a bimolecular RNA G-quadruplex consisting of a pair of two tetrads stacked 3ʹ to 5ʹ. We observe that ND11 interacts by binding on both the externally available 5ʹ and 3ʹ quartets. The CUC (loop 1) is structurally altered to enhance the 5ʹ mode of interaction. These loop residues are shifted significantly to generate a new ligand binding pocket whereas the terminal A14 residue is lifted away from the RNA G-quadruplex tetrad plane to be restacked above the bound ND11 ligand NDI core. CD analysis of this family of NDI ligands shows consistency in the spectra between the different ligands in the presence of the rPRV RNA G-quadruplex motif, reflecting a common folded topology and mode of ligand interaction. FRET melt assay confirms the strong stabilising properties of the tetrasubstituted NDI compounds and the contributions length of the substituted groups have on melt temperatures.
为了合理解释特定配体与 RNA-四联体的结合，我们研究了几种与伪狂犬病毒（PRV）非编码区相互作用的萘二亚胺配体。在此，我们报告了萘二亚胺 ND11 与来自 rPRV 的 RNA G-四叠体假定形成序列的 X 射线结构。与之前观察到的 rPRV 序列一致，ND11 组装成了双分子 RNA G-四叠体，由一对从 3'到 5'堆叠的四元组组成。我们观察到，ND11 通过与外部可用的 5'和 3'四元组结合而相互作用。CUC（环 1）的结构发生了改变，从而增强了 5'相互作用模式。这些环路残基发生了明显的位移，从而产生了一个新的配体结合口袋，而末端 A14 残基则从 RNA G-四重四元平面上移开，重新堆叠在结合 ND11 配体 NDI 核心的上方。对这一系列 NDI 配体的 CD 分析表明，在 rPRV RNA G-quadruplex 图元存在的情况下，不同配体的光谱具有一致性，这反映了一种共同的折叠拓扑结构和配体相互作用模式。FRET 熔化试验证实了四取代 NDI 化合物的强大稳定特性，以及取代基团的长度对熔化温度的影响。
{"title":"Structural descriptions of ligand interactions to RNA quadruplexes folded from the non-coding region of pseudorabies virus","authors":"Yashu Zhang , Khair Bux , Fedaa Attana , Dengguo Wei , Shozeb Haider , Gary N. Parkinson","doi":"10.1016/j.biochi.2024.06.003","DOIUrl":"10.1016/j.biochi.2024.06.003","url":null,"abstract":"<div><div>To rationalise the binding of specific ligands to RNA-quadruplex we investigated several naphthalene diimide ligands that interact with the non-coding region of Pseudorabies virus (PRV). Herein we report on the x-ray structure of the naphthalene diimide ND11 with an RNA G-quadruplex putative forming sequence from rPRV. Consistent with previously observed rPRV sequence it assembles into a bimolecular RNA G-quadruplex consisting of a pair of two tetrads stacked 3ʹ to 5ʹ. We observe that ND11 interacts by binding on both the externally available 5ʹ and 3ʹ quartets. The CUC (loop 1) is structurally altered to enhance the 5ʹ mode of interaction. These loop residues are shifted significantly to generate a new ligand binding pocket whereas the terminal A14 residue is lifted away from the RNA G-quadruplex tetrad plane to be restacked above the bound ND11 ligand NDI core. CD analysis of this family of NDI ligands shows consistency in the spectra between the different ligands in the presence of the rPRV RNA G-quadruplex motif, reflecting a common folded topology and mode of ligand interaction. FRET melt assay confirms the strong stabilising properties of the tetrasubstituted NDI compounds and the contributions length of the substituted groups have on melt temperatures.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 28-36"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141322207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.07.008
Maik Damm , Ignazio Avella , Reema Merzara , Nahla Lucchini , Jon Buldain , Frederico Corga , Abdellah Bouazza , Soumia Fahd , Roderich D. Süssmuth , Fernando Martínez-Freiría
The North African mountain viper (Vipera monticola) is a medically relevant venomous snake distributed in Morocco, Algeria, and Tunisia. Three subspecies of V. monticola, exhibiting differences in morphotypes and dietary regimes, are currently recognised: V. m. monticola, V. m. atlantica, and V. m. saintgironsi. Through the application of snake venomics, we analysed the venoms of specimens of Moroccan origin belonging to each of the three subspecies. Snake venom metalloproteinases (svMP), snake venom serine proteases (svSP), C-type lectin and C-type lectin-related proteins (CTL), and phospholipases A2 (PLA2) were predominant, with PLA2 being the most abundant toxin family overall. Disintegrins (DI) and cysteine-rich secretory proteins (CRISP) were exclusive to V. m. monticola and V. m. atlantica, while l-amino-acid oxidases (LAAO) were only found in V. m. saintgironsi. The differences detected in the venom profiles, as well as in presence/absence and relative abundances of toxin families, indicate the occurrence of intraspecific venom variation within V. monticola. The identified patterns of venom similarity between subspecies seem to align more with their phylogenetic relationships than with the reported differences in their feeding habits.
{"title":"Venom variation among the three subspecies of the North African mountain viper Vipera monticola Saint Girons 1953","authors":"Maik Damm , Ignazio Avella , Reema Merzara , Nahla Lucchini , Jon Buldain , Frederico Corga , Abdellah Bouazza , Soumia Fahd , Roderich D. Süssmuth , Fernando Martínez-Freiría","doi":"10.1016/j.biochi.2024.07.008","DOIUrl":"10.1016/j.biochi.2024.07.008","url":null,"abstract":"<div><div>The North African mountain viper (<em>Vipera monticola</em>) is a medically relevant venomous snake distributed in Morocco, Algeria, and Tunisia. Three subspecies of <em>V. monticola</em>, exhibiting differences in morphotypes and dietary regimes, are currently recognised: <em>V. m. monticola</em>, <em>V. m. atlantica</em>, and <em>V. m. saintgironsi</em>. Through the application of snake venomics, we analysed the venoms of specimens of Moroccan origin belonging to each of the three subspecies. Snake venom metalloproteinases (svMP), snake venom serine proteases (svSP), C-type lectin and C-type lectin-related proteins (CTL), and phospholipases A<sub>2</sub> (PLA<sub>2</sub>) were predominant, with PLA<sub>2</sub> being the most abundant toxin family overall. Disintegrins (DI) and cysteine-rich secretory proteins (CRISP) were exclusive to <em>V. m. monticola</em> and <em>V. m. atlantica</em>, while <span>l</span>-amino-acid oxidases (LAAO) were only found in <em>V. m. saintgironsi</em>. The differences detected in the venom profiles, as well as in presence/absence and relative abundances of toxin families, indicate the occurrence of intraspecific venom variation within <em>V. monticola</em>. The identified patterns of venom similarity between subspecies seem to align more with their phylogenetic relationships than with the reported differences in their feeding habits.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 152-160"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.08.003
Eva H. Naser , Ahmed H. Idries , Sara A.A. Elmubarak , Maha B. Dafalla , Yusria E. Abdelrahim , Entsar A. Abdalrhman , Bashir M. Ahmed , Makarim Elfadil M. Osman , Amna K.E. Awadallah , Reem M.A. Ebrahim , Ashraf O. Abdellatif , Haseeba A. Saad , Emadeldin H.E. Konozy
In the pursuit of safer and more effective treatments, there is a growing interest in plant-derived compounds, particularly lectins, because of their diverse pharmacological properties. This study focused on isolating, purifying, and characterizing lectin from Combretum glutinosum seeds (CGSLs) to assess its potential as an analgesic and antiulcer agent. CGSL extraction involved defatting and buffer extraction, followed by purification using ammonium sulfate fractionation and fetuin-agarose affinity column chromatography. The isolectins (iso-CGSLs), each consisting of 60 kDa and 57 kDa heterodimeric subunits, displayed glycoprotein properties with a 40 % neutral sugar content. They exhibited peak activity at 55 °C and remained stable for up to the fifth day at room temperature. The activity exhibited a pH dependence, peaking between 7.5 and 10.5, and all seemingly operated independently of metal ions. CGSL, at optimal doses ranging from 6 to 12 mg/kg, had significant analgesic effects on acetic acid-induced writhing and hot plate tests in mice. Evaluation using 0.7 % acetic acid resulted in notable pain reduction across all doses (P < 0.05). The analgesic effect of lectin was partially reversed by naloxone (a morphine antagonist), indicating partial involvement of the opioid receptor system. Furthermore, CGSL exhibited antiulcer effects in ethanol-induced gastric ulcer models in rats, highlighting its therapeutic potential as a natural alternative for analgesic and antiulcer treatments.
{"title":"Isolation, purification, and characterization of lectins from medicinal plant Combretum glutinosum seeds endowed with analgesic and antiulcer properties","authors":"Eva H. Naser , Ahmed H. Idries , Sara A.A. Elmubarak , Maha B. Dafalla , Yusria E. Abdelrahim , Entsar A. Abdalrhman , Bashir M. Ahmed , Makarim Elfadil M. Osman , Amna K.E. Awadallah , Reem M.A. Ebrahim , Ashraf O. Abdellatif , Haseeba A. Saad , Emadeldin H.E. Konozy","doi":"10.1016/j.biochi.2024.08.003","DOIUrl":"10.1016/j.biochi.2024.08.003","url":null,"abstract":"<div><div>In the pursuit of safer and more effective treatments, there is a growing interest in plant-derived compounds, particularly lectins, because of their diverse pharmacological properties. This study focused on isolating, purifying, and characterizing lectin from <em>Combretum glutinosum</em> seeds (CGSLs) to assess its potential as an analgesic and antiulcer agent. CGSL extraction involved defatting and buffer extraction, followed by purification using ammonium sulfate fractionation and fetuin-agarose affinity column chromatography. The isolectins (iso-CGSLs), each consisting of 60 kDa and 57 kDa heterodimeric subunits, displayed glycoprotein properties with a 40 % neutral sugar content. They exhibited peak activity at 55 °C and remained stable for up to the fifth day at room temperature. The activity exhibited a pH dependence, peaking between 7.5 and 10.5, and all seemingly operated independently of metal ions. CGSL, at optimal doses ranging from 6 to 12 mg/kg, had significant analgesic effects on acetic acid-induced writhing and hot plate tests in mice. Evaluation using 0.7 % acetic acid resulted in notable pain reduction across all doses (<em>P</em> < 0.05). The analgesic effect of lectin was partially reversed by naloxone (a morphine antagonist), indicating partial involvement of the opioid receptor system. Furthermore, CGSL exhibited antiulcer effects in ethanol-induced gastric ulcer models in rats, highlighting its therapeutic potential as a natural alternative for analgesic and antiulcer treatments.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 273-285"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.09.006
Chems Amari , Marta Carletti , Siqi Yan , Morgane Michaud , Juliette Salvaing
Lipid droplets (LDs) are organelles composed of a hydrophobic core (mostly triacylglycerols and steryl esters) delineated by a lipid monolayer and found throughout the tree of life. LDs were seen for a long time as simple energy storage organelles but recent works highlighted their versatile roles in several fundamental cellular processes, particularly during stress response. LDs biogenesis occurs in the ER and their number and size can be dynamically regulated depending on their function, e.g. during development or stress. Understanding their biogenesis and degradation mechanisms is thus essential to better apprehend their roles. LDs degradation can occur in the cytosol by lipolysis or after their internalization into lytic compartments (e.g. vacuoles or lysosomes) using diverse mechanisms that depend on the considered organism, tissue, developmental stage or environmental condition. In this review, we summarize our current knowledge on the different LDs degradation pathways in several main phyla of model organisms, unicellular or pluricellular, photosynthetic or not (budding yeast, mammals, land plants and microalgae). We highlight the conservation of the main degradation pathways throughout evolution, but also the differences between organisms, or inside an organism between different organs. Finally, we discuss how this comparison can help to shed light on relationships between LDs degradation pathways and LDs functions.
{"title":"Lipid droplets degradation mechanisms from microalgae to mammals, a comparative overview","authors":"Chems Amari , Marta Carletti , Siqi Yan , Morgane Michaud , Juliette Salvaing","doi":"10.1016/j.biochi.2024.09.006","DOIUrl":"10.1016/j.biochi.2024.09.006","url":null,"abstract":"<div><div>Lipid droplets (LDs) are organelles composed of a hydrophobic core (mostly triacylglycerols and steryl esters) delineated by a lipid monolayer and found throughout the tree of life. LDs were seen for a long time as simple energy storage organelles but recent works highlighted their versatile roles in several fundamental cellular processes, particularly during stress response. LDs biogenesis occurs in the ER and their number and size can be dynamically regulated depending on their function, <em>e.g.</em> during development or stress. Understanding their biogenesis and degradation mechanisms is thus essential to better apprehend their roles. LDs degradation can occur in the cytosol by lipolysis or after their internalization into lytic compartments (<em>e.g</em>. vacuoles or lysosomes) using diverse mechanisms that depend on the considered organism, tissue, developmental stage or environmental condition. In this review, we summarize our current knowledge on the different LDs degradation pathways in several main phyla of model organisms, unicellular or pluricellular, photosynthetic or not (budding yeast, mammals, land plants and microalgae). We highlight the conservation of the main degradation pathways throughout evolution, but also the differences between organisms, or inside an organism between different organs. Finally, we discuss how this comparison can help to shed light on relationships between LDs degradation pathways and LDs functions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 19-34"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.06.009
Aleksandra Bednarz , Rebecca Torp Rosendal , Line Mørkholt Lund , Victoria Birkedal
G-quadruplexes (G4s) are helical four-stranded nucleic acid structures that can form in guanine-rich sequences, which are mostly found in functional cellular regions, such as telomeres, promoters, and DNA replication origins. Great efforts are being made to target these structures towards the development of specific small molecule G4 binders for novel anti-cancer, neurological, and viral therapies. Here, we introduce an optical assay based on quenching of the intrinsic fluorescence of DNA G-quadruplexes for assessing and comparing the G4 binding affinity of various small molecule ligands in solutions. We show that the approach allows direct quantification of ligand binding to distinctive G4 topologies. We believe that this method will facilitate quick and reliable evaluation of small molecule G4 ligands and support their development.
G-quadruplexes (G4s) 是一种螺旋状四链核酸结构，可在富含鸟嘌呤的序列中形成，主要存在于端粒、启动子和 DNA 复制源等细胞功能区。目前，人们正努力以这些结构为靶点，开发用于新型抗癌、神经和病毒疗法的特异性小分子 G4 结合剂。在这里，我们介绍了一种基于淬灭 DNA G-四联体固有荧光的光学检测方法，用于评估和比较各种小分子配体在溶液中的 G4 结合亲和力。我们的研究表明，这种方法可以直接量化配体与不同 G4 拓扑的结合。我们相信，这种方法将有助于快速、可靠地评估小分子 G4 配体，并支持它们的开发。
{"title":"Probing G-quadruplex-ligand binding using DNA intrinsic fluorescence","authors":"Aleksandra Bednarz , Rebecca Torp Rosendal , Line Mørkholt Lund , Victoria Birkedal","doi":"10.1016/j.biochi.2024.06.009","DOIUrl":"10.1016/j.biochi.2024.06.009","url":null,"abstract":"<div><div>G-quadruplexes (G4s) are helical four-stranded nucleic acid structures that can form in guanine-rich sequences, which are mostly found in functional cellular regions, such as telomeres, promoters, and DNA replication origins. Great efforts are being made to target these structures towards the development of specific small molecule G4 binders for novel anti-cancer, neurological, and viral therapies. Here, we introduce an optical assay based on quenching of the intrinsic fluorescence of DNA G-quadruplexes for assessing and comparing the G4 binding affinity of various small molecule ligands in solutions. We show that the approach allows direct quantification of ligand binding to distinctive G4 topologies. We believe that this method will facilitate quick and reliable evaluation of small molecule G4 ligands and support their development.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 61-67"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.09.007
Amazigh Hamaï, Guillaume Drin
Lipids, which are highly diverse, are finely distributed between organelle membranes and the plasma membrane (PM) of eukaryotic cells. As a result, each compartment has its own lipid composition and molecular identity, which is essential for the functional fate of many proteins. This distribution of lipids depends on two main processes: lipid synthesis, which takes place in different subcellular regions, and the transfer of these lipids between and across membranes. This review will discuss the proteins that carry lipids throughout the cytosol, called LTPs (Lipid Transfer Proteins). More than the modes of action or biological roles of these proteins, we will focus on the in vitro strategies employed during the last 60 years to address a critical question: What are the lipid ligands of these LTPs? We will describe the extent to which these strategies, combined with structural data and investigations in cells, have made it possible to discover proteins, namely ORPs, Sec14, PITPs, STARDs, Ups/PRELIs, START-like, SMP-domain containing proteins, and bridge-like LTPs, which compose some of the main eukaryotic LTP families, and their lipid ligands. We will see how these approaches have played a central role in cell biology, showing that LTPs can connect distant metabolic branches, modulate the composition of cell membranes, and even create new subcellular compartments.
{"title":"Specificity of lipid transfer proteins: An in vitro story","authors":"Amazigh Hamaï, Guillaume Drin","doi":"10.1016/j.biochi.2024.09.007","DOIUrl":"10.1016/j.biochi.2024.09.007","url":null,"abstract":"<div><div>Lipids, which are highly diverse, are finely distributed between organelle membranes and the plasma membrane (PM) of eukaryotic cells. As a result, each compartment has its own lipid composition and molecular identity, which is essential for the functional fate of many proteins. This distribution of lipids depends on two main processes: lipid synthesis, which takes place in different subcellular regions, and the transfer of these lipids between and across membranes. This review will discuss the proteins that carry lipids throughout the cytosol, called LTPs (Lipid Transfer Proteins). More than the modes of action or biological roles of these proteins, we will focus on the <em>in vitro</em> strategies employed during the last 60 years to address a critical question: What are the lipid ligands of these LTPs? We will describe the extent to which these strategies, combined with structural data and investigations in cells, have made it possible to discover proteins, namely ORPs, Sec14, PITPs, STARDs, Ups/PRELIs, START-like, SMP-domain containing proteins, and bridge-like LTPs, which compose some of the main eukaryotic LTP families, and their lipid ligands. We will see how these approaches have played a central role in cell biology, showing that LTPs can connect distant metabolic branches, modulate the composition of cell membranes, and even create new subcellular compartments.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 85-110"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.09.003
Khaled Tighanimine
Cellular senescence is a response that irreversibly arrests stressed cells thus providing a potent tumor suppressor mechanism. In parallel, senescent cells exhibit an immunogenic secretome called SASP (senescence-associated secretory phenotype) that impairs tissue homeostasis and is involved in numerous age-related diseases. Senescence establishment is achieved through the unfolding of a profound transcriptional reprogramming together with morphological changes. These alterations are accompanied by important metabolic adaptations characterized by biosynthetic pathways reshuffling and lipid remodeling. In this mini-review we highlight the intricate links between lipid metabolism and the senescence program and we discuss the potential interventions on lipid pathways that can alleviate the senescence burden.
{"title":"Lipid remodeling in context of cellular senescence","authors":"Khaled Tighanimine","doi":"10.1016/j.biochi.2024.09.003","DOIUrl":"10.1016/j.biochi.2024.09.003","url":null,"abstract":"<div><div>Cellular senescence is a response that irreversibly arrests stressed cells thus providing a potent tumor suppressor mechanism. In parallel, senescent cells exhibit an immunogenic secretome called SASP (senescence-associated secretory phenotype) that impairs tissue homeostasis and is involved in numerous age-related diseases. Senescence establishment is achieved through the unfolding of a profound transcriptional reprogramming together with morphological changes. These alterations are accompanied by important metabolic adaptations characterized by biosynthetic pathways reshuffling and lipid remodeling. In this mini-review we highlight the intricate links between lipid metabolism and the senescence program and we discuss the potential interventions on lipid pathways that can alleviate the senescence burden.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 47-52"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.07.014
Fahmida Sultana, Ajit Ghosh
The mineral iron plays a crucial role in facilitating the optimal functioning of numerous biological processes within the cellular environment. These processes involve the transportation of oxygen, energy production, immune system functioning, cognitive abilities, and muscle function. However, it is crucial to note that excessive levels of iron can result in oxidative damage within cells, primarily through Fenton reactions. Iron availability and toxicity present significant challenges that have been addressed through evolution. Ferritin is an essential protein that stores iron and is divided into different subfamilies, including DNA-binding proteins under starvation (Dps), bacterioferritin, and classical ferritin. Ferritin plays a critical role in maintaining cellular balance and protecting against oxidative damage. This study delves into ferritin's evolutionary dynamics across diverse taxa, emphasizing structural features and regulatory mechanisms. Insights into ferritin's evolution and functional diversity are gained through phylogenetic and structural analysis in bacterial Dps, bacterioferritin, and classical ferritin proteins. Additionally, the involvement of ferritin in plant stress responses and development is explored. Analysis of ferritin gene expression across various developmental stages and stress conditions provides insights into its regulatory roles. This comprehensive exploration enhances our understanding of ferritin's significance in plant biology, offering insights into its evolutionary history, structural diversity, and protective mechanisms against oxidative stress.
矿物质铁在促进细胞环境中许多生物过程的最佳运作方面发挥着至关重要的作用。这些过程涉及氧气运输、能量生产、免疫系统功能、认知能力和肌肉功能。然而，必须注意的是，过量的铁会导致细胞内的氧化损伤，主要是通过芬顿反应。铁的可用性和毒性带来了巨大的挑战，而这些挑战已通过进化得到解决。铁蛋白是一种储存铁的重要蛋白质，分为不同的亚家族，包括饥饿状态下的 DNA 结合蛋白（Dps）、细菌铁蛋白和经典铁蛋白。它在维持细胞平衡和防止氧化损伤方面发挥着至关重要的作用。本研究深入探讨了铁蛋白在不同类群中的进化动态，强调了其结构特征和调控机制。通过对细菌 Dps、细菌铁蛋白和经典铁蛋白的系统发育和结构分析，深入了解铁蛋白的进化和功能多样性。此外，还探讨了铁蛋白在植物胁迫反应和发育中的参与。通过分析铁蛋白基因在不同发育阶段和胁迫条件下的表达，可以深入了解铁蛋白的调控作用。这一全面的探索增强了我们对铁蛋白在植物生物学中的意义的理解，为我们深入了解铁蛋白的进化历史、结构多样性以及对氧化应激的保护机制提供了帮助。
{"title":"Exploring the evolutionary landscape and structural resonances of ferritin with insights into functional significance in plant","authors":"Fahmida Sultana, Ajit Ghosh","doi":"10.1016/j.biochi.2024.07.014","DOIUrl":"10.1016/j.biochi.2024.07.014","url":null,"abstract":"<div><div>The mineral iron plays a crucial role in facilitating the optimal functioning of numerous biological processes within the cellular environment. These processes involve the transportation of oxygen, energy production, immune system functioning, cognitive abilities, and muscle function. However, it is crucial to note that excessive levels of iron can result in oxidative damage within cells, primarily through Fenton reactions. Iron availability and toxicity present significant challenges that have been addressed through evolution. Ferritin is an essential protein that stores iron and is divided into different subfamilies, including DNA-binding proteins under starvation (Dps), bacterioferritin, and classical ferritin. Ferritin plays a critical role in maintaining cellular balance and protecting against oxidative damage. This study delves into ferritin's evolutionary dynamics across diverse taxa, emphasizing structural features and regulatory mechanisms. Insights into ferritin's evolution and functional diversity are gained through phylogenetic and structural analysis in bacterial Dps, bacterioferritin, and classical ferritin proteins. Additionally, the involvement of ferritin in plant stress responses and development is explored. Analysis of ferritin gene expression across various developmental stages and stress conditions provides insights into its regulatory roles. This comprehensive exploration enhances our understanding of ferritin's significance in plant biology, offering insights into its evolutionary history, structural diversity, and protective mechanisms against oxidative stress.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 217-230"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.biochi.2024.06.011
Maxim Shkurnikov , Darya Averinskaya , Elena Stekolshchikova , Anna Serkina , Alexandra Razumovskaya , Maria Silkina , Ivan Antipenko , Julia Makarova , Ekaterina Evtushenko , Sergey Nikulin , Alexander Tonevitsky
Breast cancer recurrence is associated with the growth of disseminated cancer cells that separate from the primary tumor before surgical treatment and hormonal therapy and form a metastatic niche in distant organs. We previously demonstrated that IGFBP6 expression is associated with the risk of early relapse of luminal breast cancer. Knockdown of IGFBP6 in MDA-MB-231 breast cancer cells increased their invasiveness, proliferation, and metastatic potential. In addition, the knockdown of IGFBP6 leads to impaired lipid metabolism. In this study, we demonstrated that the knockdown of the IGFBP6 gene, a highly selective inhibitor of IGF-II, led to a significant decline in the number of secreted extracellular vesicles (EVs) and altered cholesterol metabolism in MDA-MB-231 cells. Knockdown of IGFBP6 led to a decrease in the essential proteins responsible for the biogenesis of cholesterol LDLR and LSS, which reduced the amount by more than 13 times. In addition, the knockdown of IGFBP6 led to a possible change in the profile of adhesion molecules on the surface of EVs. The expression of L1CAM, IGSF3, EpCAM, CD24, and CD44 decreased, and the expression of EGFR increased. We can conclude that the negative prognostic value of low expression of this gene could be associated with increased activity of IGF2 in tumor-associated fibroblasts due to low secretion of IGFBP6 by tumor cells. In addition, changing the profile of adhesion molecules on the surface of tumor EVs may contribute to the more efficient formation of metastatic niches.
{"title":"IGFBP6 regulates extracellular vesicles formation via cholesterol abundance in MDA-MB-231 cells","authors":"Maxim Shkurnikov , Darya Averinskaya , Elena Stekolshchikova , Anna Serkina , Alexandra Razumovskaya , Maria Silkina , Ivan Antipenko , Julia Makarova , Ekaterina Evtushenko , Sergey Nikulin , Alexander Tonevitsky","doi":"10.1016/j.biochi.2024.06.011","DOIUrl":"10.1016/j.biochi.2024.06.011","url":null,"abstract":"<div><div><span><span>Breast cancer recurrence is associated with the growth of disseminated cancer cells that separate from the primary tumor before surgical treatment and hormonal therapy and form a metastatic niche in distant organs. We previously demonstrated that IGFBP6<span><span> expression is associated with the risk of early relapse of luminal breast cancer. Knockdown of IGFBP6 in MDA-MB-231 breast cancer cells increased their invasiveness, proliferation, and metastatic potential. In addition, the knockdown of IGFBP6 leads to impaired lipid metabolism. In this study, we demonstrated that the knockdown of the IGFBP6 gene, a highly selective inhibitor of IGF-II, led to a significant decline in the number of secreted extracellular vesicles (EVs) and altered cholesterol metabolism in MDA-MB-231 cells. Knockdown of IGFBP6 led to a decrease in the essential proteins responsible for the biogenesis of cholesterol LDLR and LSS, which reduced the amount by more than 13 times. In addition, the knockdown of IGFBP6 led to a possible change in the profile of </span>adhesion molecules on the surface of EVs. The expression of L1CAM, IGSF3, </span></span>EpCAM<span><span>, CD24, and </span>CD44 decreased, and the expression of </span></span>EGFR increased. We can conclude that the negative prognostic value of low expression of this gene could be associated with increased activity of IGF2 in tumor-associated fibroblasts due to low secretion of IGFBP6 by tumor cells. In addition, changing the profile of adhesion molecules on the surface of tumor EVs may contribute to the more efficient formation of metastatic niches.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"227 ","pages":"Pages 77-85"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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