Biochimie最新文献_第7页

Targeting autophagy via mitochondrial uncoupling: Discovery of novel serratin derivative as a potential therapeutic for Parkinson's disease 通过线粒体解偶联靶向自噬：发现新的serratn衍生物作为帕金森病的潜在治疗药物。

IF 3 3区生物学

Biochimie Pub Date : 2026-01-01 Epub Date: 2025-10-15 DOI: 10.1016/j.biochi.2025.10.011

Alexander Yu Rudenko , Ekaterina А. Guseva , Ratislav M. Ozhiganov , Boris P. Myasnikov , Maria V. Belopolskaya , Olga V. Fadeeva , Elena О. Morgun , Olga A. Averina , Elena A. Tukhovskaya , Gulsara A. Slashcheva , Igor A. Dyachenko , Elena I. Marusich , Mariia Mokhina , Rose-Lys Zaranaina , Yuriy A. Ikhalaynen , Igor A. Rodin , Ljudmila S. Khailova , Yuri N. Antonenko , Vladimir I. Polshakov , Maxim L. Lovat , Petr V. Sergiev

{"title":"Targeting autophagy via mitochondrial uncoupling: Discovery of novel serratin derivative as a potential therapeutic for Parkinson's disease","authors":"Alexander Yu Rudenko , Ekaterina А. Guseva , Ratislav M. Ozhiganov , Boris P. Myasnikov , Maria V. Belopolskaya , Olga V. Fadeeva , Elena О. Morgun , Olga A. Averina , Elena A. Tukhovskaya , Gulsara A. Slashcheva , Igor A. Dyachenko , Elena I. Marusich , Mariia Mokhina , Rose-Lys Zaranaina , Yuriy A. Ikhalaynen , Igor A. Rodin , Ljudmila S. Khailova , Yuri N. Antonenko , Vladimir I. Polshakov , Maxim L. Lovat , Petr V. Sergiev","doi":"10.1016/j.biochi.2025.10.011","DOIUrl":"10.1016/j.biochi.2025.10.011","url":null,"abstract":"<div><div>Autophagy, a highly conserved cellular degradation pathway, plays a critical role in maintaining cellular homeostasis across eukaryotes. Dysregulation of autophagy has been implicated in numerous diseases, including neurodegenerative disorders such as Parkinson's disease. Although natural compounds like urolithin A and its synthetic analogue serratin (AN2) have been shown to induce autophagy, their limited potency and safety profiles necessitate the development of improved alternatives. In this study, a library of 27 novel AN2 analogues was synthesized and screened for autophagy-inducing activity. Among them, ORA471 emerged as a lead compound, exhibiting superior autophagy and mitophagy activation compared to AN2, along with reduced cytotoxicity in human fibroblast (VA-13) and neuroblastoma (SH-SY5Y) cell lines. Mechanistic investigations revealed that ORA471 induces autophagy primarily via the AMPK/ULK1 signaling pathway and acts as a mitochondrial uncoupler, dissipating membrane potential and enhancing respiration in isolated rat liver mitochondria. <em>In vivo</em>, ORA471 demonstrated low toxicity in <em>Caenorhabditis elegans</em>, zebrafish (<em>Danio rerio</em>), and mice (maximum tolerated dose: 300 mg/kg). Notably, it significantly improved motor function in a zebrafish model of MPTP-induced Parkinson's disease without eliciting adverse effects. These findings highlight ORA471 as a promising therapeutic candidate for the treatment of autophagy-related disorders, particularly Parkinson's disease.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 125-136"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314241","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}

引用次数: 0

Novel alternative transcripts of TLR8 and TLR9 reveal evolutionary pressure to conserve protein structure TLR8和TLR9的新转录本揭示了保护蛋白质结构的进化压力。

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-09-05 DOI: 10.1016/j.biochi.2025.09.003

Jorge Martinez-Laso , Isabel Cervera , María José Muñoz-Gómez , Clara Sánchez-Menéndez , Ana Salamanca-Soto , Montserrat Torres , Mayte Coiras

{"title":"Novel alternative transcripts of TLR8 and TLR9 reveal evolutionary pressure to conserve protein structure","authors":"Jorge Martinez-Laso , Isabel Cervera , María José Muñoz-Gómez , Clara Sánchez-Menéndez , Ana Salamanca-Soto , Montserrat Torres , Mayte Coiras","doi":"10.1016/j.biochi.2025.09.003","DOIUrl":"10.1016/j.biochi.2025.09.003","url":null,"abstract":"<div><div>TLR8 and TLR9 are innate immune receptors belonging to the TLR family that are essential for viral recognition and early immune activation. Their dysfunction is linked to increased susceptibility to infections. TLR8 detects viral single- and double-stranded RNA, while TLR9 recognizes viral DNA molecules with CpG motifs. Six TLR8 alternative transcripts (V1, V2, V5, V6, V7, and V8) and nine TLR9 (V1, A, B, C, D, E, V8, V9, and V10) have been previously described in humans. In the present study, we have performed a comprehensive analysis of TLR8 and TLR9 transcripts in a healthy population and two new TLR8 transcripts (V3 and V4) and four new TLR9 transcripts (V2, V5, V6, and V7) were found. The main mechanisms for the generation of different mRNA variants were the insertion of non-coding regions and the loss of whole or partial exons. These changes result in the loss or insertion of new amino acids but only modify the initial leucine-rich repeat (LRR) region and preserve the rest of the receptor's complete structure. From the results obtained, we can deduce that there seems to be a strong evolutionary drive to maintain TLR8 and TLR9 functionality, unlike other innate immune response receptors.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 261-264"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016936","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}

引用次数: 0

Inside front cover-EDB 内部前盖- edb

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-11-27 DOI: 10.1016/S0300-9084(25)00274-3

引用次数: 0

Sterol biosynthesis and phytosterol bioconversion in Crassostrea gigas larvae: new evidence from mass-balance feeding studies 长牡蛎幼虫的甾醇生物合成和植物甾醇生物转化：来自质量平衡摄食研究的新证据。

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-05-16 DOI: 10.1016/j.biochi.2025.05.005

Fiz da Costa , Margaux Mathieu-Resuge , Fabienne Le Grand , Claudie Quéré , Gabriel V. Markov , Gary H. Wikfors , Philippe Soudant

{"title":"Sterol biosynthesis and phytosterol bioconversion in Crassostrea gigas larvae: new evidence from mass-balance feeding studies","authors":"Fiz da Costa , Margaux Mathieu-Resuge , Fabienne Le Grand , Claudie Quéré , Gabriel V. Markov , Gary H. Wikfors , Philippe Soudant","doi":"10.1016/j.biochi.2025.05.005","DOIUrl":"10.1016/j.biochi.2025.05.005","url":null,"abstract":"<div><div>Dietary sterols are important for bivalve larval growth and survival. The aim of the study was to determine quantitatively sterol incorporation and synthesis in Pacific oyster <em>Crassostrea gigas</em> larvae by means of a mass-balance approach. The flow-through larval rearing technique allowed accurate quantification of microalgal ingestion and consequently of sterol ingestion. Sterol incorporation was calculated using the sterol composition of the larvae between 2 sample points. Two sets of experiments were done using two cultured microalgae: <em>Tisochrysis lutea</em> (T) and <em>Chaetoceros neogracile</em> (Cg) as mono- and bi-specific diets (TCg). Accumulation of tissue sterols in oyster larvae, in addition to those present in the diet, indicate that <em>C. gigas</em> larvae appear to have the ability to synthetize sterols <em>de novo</em> under low dietary sterol supply, e.g., when fed the T diet. Sterol synthesis was dependent upon sterol dietary supply; larvae fed T exhibited greater sterol incorporation at the pediveliger stage than larvae fed TCg. Larval sterol compositions under the different dietary regimes indicate likely bioconversion pathways modifying dietary sterols. Larvae fed T bioconverted dietary brassicasterol mainly to cholesterol <em>via</em> a 22-dehydrocholesterol intermediate. Brassicasterol was also actively synthetized in larvae fed T and TCg, suggesting a possible metabolic role of this sterol in <em>C. gigas</em> larvae. Apparent desmosterol synthesis under all experimental conditions suggests a role as a membrane component or as an intermediate in cholesterol synthesis. Our data also indicate that <em>C. gigas</em> larvae require approximately 13 ng cholesterol larvae<sup>−1</sup> to achieve competence for metamorphosis. This mass-balance approach will allow the determination of other biochemical requirements in larval nutrition.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 51-59"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096198","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}

引用次数: 0

Exploring therapeutic targets with the HMM-SA structural alphabet: Methods, tools, and application to HIV-2 protease 用HMM-SA结构字母表探索治疗靶点：方法、工具和对HIV-2蛋白酶的应用。

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-08-08 DOI: 10.1016/j.biochi.2025.08.001

Anne-Claude Camproux, Marine Baillif, Léa Dufay, Leslie Regad

{"title":"Exploring therapeutic targets with the HMM-SA structural alphabet: Methods, tools, and application to HIV-2 protease","authors":"Anne-Claude Camproux, Marine Baillif, Léa Dufay, Leslie Regad","doi":"10.1016/j.biochi.2025.08.001","DOIUrl":"10.1016/j.biochi.2025.08.001","url":null,"abstract":"<div><div>The rapid expansion of available three-dimensional protein structures—derived from both experimental techniques and bioinformatic predictions—offers unprecedented opportunities for drug discovery, particularly for targets that have historically been difficult to characterize. However, the effective analysis of these increasingly complex and voluminous structural datasets remains a major challenge. Efficient representations of protein conformations are essential to facilitate large-scale comparison, structural classification, and functional interpretation in therapeutic contexts. The concept of structural alphabets, introduced by Pr S. Hazout in 1999, provides a robust and scalable framework to represent local protein backbone conformations using a limited set of recurring structural motifs. This representation enables a one-dimensional encoding of three-dimensional protein structures that retains essential geometric features beyond secondary structure, while allowing systematic and interpretable analyses. In this review, we focus on HMM-SA, a structural alphabet constructed using a hidden Markov model. HMM-SA defines 27 structural motifs, including 18 regions specifically dedicated to loops, and captures the statistical dependencies between them. We present a detailed overview of the HMM-SA framework, and of the computational tools derived from this structural alphabet, developed to explore protein function, conformational variability, and the structural determinants of molecular recognition. The utility of HMM-SA is illustrated through a case study on HIV-2 protease (PR2), a critical enzyme in antiretroviral drug development. By analyzing PR2 structural asymmetry, ligand-induced conformational changes, and mutation-driven alterations, we highlight the ability of HMM-SA–based methods to identify key structural features involved in ligand specificity and resistance mechanisms, thereby advancing therapeutic target analysis.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 39-57"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818644","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}

引用次数: 0

Human CXCL17 binds and activates fish GPR25 orthologs 人类CXCL17结合并激活鱼类GPR25同源物。

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-09-17 DOI: 10.1016/j.biochi.2025.09.009

Wen-Feng Hu , Juan-Juan Wang , Jie Yu, Jun-Jie Yao, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo

{"title":"Human CXCL17 binds and activates fish GPR25 orthologs","authors":"Wen-Feng Hu , Juan-Juan Wang , Jie Yu, Jun-Jie Yao, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo","doi":"10.1016/j.biochi.2025.09.009","DOIUrl":"10.1016/j.biochi.2025.09.009","url":null,"abstract":"<div><div>C-X-C motif chemokine ligand 17 (CXCL17) functions as a chemoattractant, though its receptor has been controversial. Recent independent studies, including our own, identified CXCL17 as an agonist for the orphan G protein-coupled receptor 25 (GPR25). While GPR25 orthologs are found across fishes to mammals, CXCL17 orthologs appear to be mammalian-specific, leaving the endogenous ligand for non-mammalian GPR25 orthologs unknown. This study unexpectedly found that human CXCL17 exhibits high activity towards GPR25 orthologs from the zebrafish (<em>Danio rerio</em>) and coelacanth (<em>Latimeria chalumnae</em>). Recombinant human CXCL17 efficiently activated both fish GPR25 orthologs in a NanoLuc Binary Technology (NanoBiT)-based β-arrestin recruitment assay, and induced chemotactic movement in transfected human embryonic kidney (HEK) 293T cells expressing fish GPR25. A human CXCL17 mutant lacking three C-terminal residues showed no such effect. A NanoBiT-based binding assay revealed that a SmBiT-tagged human CXCL17 C-terminal fragment specifically bound to secretory large NanoLuc fragment (sLgBiT)-fused fish GPR25 orthologs. Fish GPR25 orthologs had significantly higher cell surface expression in transfected HEK293T cells compared to human GPR25, improving β-arrestin recruitment assay data quality. Despite approximately 400 million years of divergence between humans and fishes, the high activity of human CXCL17 on fish GPR25 orthologs suggests that the CXCL17–GPR25 pair may be conserved across all vertebrates, even though non-mammalian CXCL17 orthologs remain unidentified.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 244-251"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093078","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}

引用次数: 0

Microbial degradation of hydrocarbons from petroleum assisted by biosurfactants: Pathways and bioremediation potential 生物表面活性剂对石油烃类的微生物降解：途径和生物修复潜力。

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.biochi.2025.09.011

Jiaxin Cui, Peter Dörmann

{"title":"Microbial degradation of hydrocarbons from petroleum assisted by biosurfactants: Pathways and bioremediation potential","authors":"Jiaxin Cui, Peter Dörmann","doi":"10.1016/j.biochi.2025.09.011","DOIUrl":"10.1016/j.biochi.2025.09.011","url":null,"abstract":"<div><div>Petroleum pollution from oil extraction, transportation, and industrial activities poses significant threats to marine ecosystems and socioeconomic stability due to the high toxicity of alkanes and polycyclic aromatic hydrocarbons (PAHs) to many organisms. Traditional remediation methods, including physical removal and chemical oxidation, are often costly and ecologically disruptive. Microbial degradation, facilitated by hydrocarbonoclastic bacteria like <em>Pseudomonas aeruginosa</em> and <em>Alcanivorax borkumensis</em>, offers a sustainable alternative by converting hydrocarbons into non-toxic CO<sub>2</sub> and water. This review examines the degradation pathways of aliphatic and aromatic hydrocarbons by these bacteria, highlighting key enzymatic mechanisms and the pivotal role of biosurfactants—specifically rhamnolipids, and glycine-glucolipid—in enhancing hydrocarbon bioavailability. It also delves into the biosynthesis of these biosurfactants, along with the involvement of non-ribosomal peptide synthetases (NRPS) in producing lipopeptide biosurfactants such as surfactin. Additionally, the review addresses the challenges associated with scaling up biosurfactant production for bioremediation applications. Through a synopsis of recent research, this work proposes strategies to optimize biosurfactant efficacy, contributing to environmental sustainability and advancing the field of microbial ecology.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 103-119"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115422","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}

引用次数: 0

Lipids: from sea to fork 社论的特别问题«脂从海洋到叉»。

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-11-05 DOI: 10.1016/j.biochi.2025.11.001

Hubert Schaller, Philippe Soudant

引用次数: 0

Inside front cover-EDB 内部前盖- edb

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-11-28 DOI: 10.1016/S0300-9084(25)00285-8

引用次数: 0

Structurally diverse herbicides inhibit β-keto-acyl-CoA synthases from monocotyledonous and dicotyledonous plant species 摘要结构多样的除草剂抑制单子叶和双子叶植物中β-酮酰基辅酶a合成酶。

IF 3 3区生物学

Biochimie Pub Date : 2025-12-01 Epub Date: 2025-07-08 DOI: 10.1016/j.biochi.2025.07.007

Claire Le Ruyet , Stéphanie Pascal , Gerlinde Usunow , Pierre Van Delft , Didier Thoraval , François Doignon , Frédéric Domergue , Peter Luemmen , Jérôme Joubès

{"title":"Structurally diverse herbicides inhibit β-keto-acyl-CoA synthases from monocotyledonous and dicotyledonous plant species","authors":"Claire Le Ruyet , Stéphanie Pascal , Gerlinde Usunow , Pierre Van Delft , Didier Thoraval , François Doignon , Frédéric Domergue , Peter Luemmen , Jérôme Joubès","doi":"10.1016/j.biochi.2025.07.007","DOIUrl":"10.1016/j.biochi.2025.07.007","url":null,"abstract":"<div><div><span><span>Very-long-chain fatty acids (VLCFA) serve as precursors for various lipids that play crucial physiological and structural roles in plants. The β-keto-acyl-CoA </span>synthase<span><span> (KCS) catalyzes the initial step of VLCFA elongation and determines the chain-length substrate specificity of the fatty acid </span>elongase<span> complex. Following an extensive phylogenetic analysis, 28 KCS genes from various plant species, including 17 functionally uncharacterized genes, were expressed in </span></span></span><span><span>Saccharomyces cerevisiae</span></span>, and their VLCFAs profiles were analyzed using gas chromatography-mass spectrometry. Yeast expressing active KCS were subsequently exposed <em>in vivo</em><span><span> to various Group 15 herbicides to investigate their mode of action and selectivity. These experiments revealed differential sensitivities of KCS enzymes to benfuresate, cafenstrole, flufenacet, pyroxasulfone, and metazachlor, while endogenous </span>VLCFA synthesis in yeast, which relies on Elop-type elongases, remained unaffected. Furthermore, to address a significant gap in understanding the inhibitory potency of Group 15 herbicides, we developed an </span><em>in vitro</em><span> enzymatic assay based on the quantification of the 3-oxo-products generated during the KCS-catalyzed reaction using high-performance liquid chromatography-mass spectrometry coupled with UV detection. This novel biochemical approach enabled the evaluation of inhibitor potency as well as the kinetic characterization of both established and newly identified KCS enzyme inhibitors.</span></div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 120-132"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610599","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}

引用次数: 0