Pub Date : 2025-12-01Epub Date: 2025-07-10DOI: 10.1016/j.biochi.2025.07.013
Isabelle Callebaut, Jean-Paul Mornon
Hydrophobic Cluster Analysis (HCA) adds secondary structure information to the analysis of protein amino acid sequence. Focusing on the elementary building blocks of protein folds, this approach has proved to be a powerful tool for detecting distant (hidden) relationships between proteins. At a time when huge masses of data are now available, both in terms of protein sequences and models of three-dimensional structures, it still constitutes a relevant tool for analyzing structural features at the scale of whole proteomes, enabling, among other things, to characterize the continuum between disorder and order and to explore the characteristics of protein dark matter. The aim of this mini-review is to provide a brief overview of this approach, describing its principles and achievements, recent developments and future prospects.
{"title":"Hydrophobic cluster analysis at protein and proteome scales","authors":"Isabelle Callebaut, Jean-Paul Mornon","doi":"10.1016/j.biochi.2025.07.013","DOIUrl":"10.1016/j.biochi.2025.07.013","url":null,"abstract":"<div><div>Hydrophobic Cluster Analysis (HCA) adds secondary structure information to the analysis of protein amino acid sequence. Focusing on the elementary building blocks of protein folds, this approach has proved to be a powerful tool for detecting distant (hidden) relationships between proteins. At a time when huge masses of data are now available, both in terms of protein sequences and models of three-dimensional structures, it still constitutes a relevant tool for analyzing structural features at the scale of whole proteomes, enabling, among other things, to characterize the continuum between disorder and order and to explore the characteristics of protein dark matter. The aim of this mini-review is to provide a brief overview of this approach, describing its principles and achievements, recent developments and future prospects.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 27-31"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621463","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 : 2025-12-01Epub Date: 2025-09-16DOI: 10.1016/j.biochi.2025.09.007
Mickael Péron , Mathilde Bertrand , Elodie Baranek , Maud Martinat , Philippe Soudant , Marie Vagner , Jérôme Roy
N-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential molecules to fish physiology, influencing their development, metabolism, immunity, behavior, and reproduction. However, fish have a limited ability to synthesize these fatty acids endogenously, and must obtain them through diet. The dietary availability of these molecules is increasingly challenged by both ecological and aquaculture constraints linked to climate change and to sustainability of ressources (e.g. fisheries). Currently, global changes – including ocean warming - may reduce the availability of these fatty acids in marine food webs, raising concerns for fish population dynamics and aquaculture sustainability that still largely depends on forage fish. In this review, we first summarize the metabolic pathways and tissue distribution of n-3 LC PUFA in freshwater and marine fish, highlighting differences in bioconversion capacities. We then explore the physiological and behavioral consequences of varying dietary n-3 LC PUFA levels in aquaculture feeds and natural environments, including effects on growth, locomotion, cognition, metabolic performance, oxidative status, immune response, and reproductive investment. We also review current alternatives to fish meal and fish oil, such as plant, insect, microbial, and genetically modified sources, and discuss their potential to meet fish nutritional needs. Altogether, this synthesis underscores the current challenge of n-3 LC PUFA dietary shortage for fish health, aquaculture production and nutritional security of human population, and identifies knowledge gaps that must be addressed to ensure both ecological resilience and sustainable aquaculture development in a rapidly changing world.
{"title":"N-3 long-chain polyunsaturated fatty acids in fish physiology: From aquaculture to economic, ecological and public health challenges","authors":"Mickael Péron , Mathilde Bertrand , Elodie Baranek , Maud Martinat , Philippe Soudant , Marie Vagner , Jérôme Roy","doi":"10.1016/j.biochi.2025.09.007","DOIUrl":"10.1016/j.biochi.2025.09.007","url":null,"abstract":"<div><div>N-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential molecules to fish physiology, influencing their development, metabolism, immunity, behavior, and reproduction. However, fish have a limited ability to synthesize these fatty acids endogenously, and must obtain them through diet. The dietary availability of these molecules is increasingly challenged by both ecological and aquaculture constraints linked to climate change and to sustainability of ressources (e.g. fisheries). Currently, global changes – including ocean warming - may reduce the availability of these fatty acids in marine food webs, raising concerns for fish population dynamics and aquaculture sustainability that still largely depends on forage fish. In this review, we first summarize the metabolic pathways and tissue distribution of n-3 LC PUFA in freshwater and marine fish, highlighting differences in bioconversion capacities. We then explore the physiological and behavioral consequences of varying dietary n-3 LC PUFA levels in aquaculture feeds and natural environments, including effects on growth, locomotion, cognition, metabolic performance, oxidative status, immune response, and reproductive investment. We also review current alternatives to fish meal and fish oil, such as plant, insect, microbial, and genetically modified sources, and discuss their potential to meet fish nutritional needs. Altogether, this synthesis underscores the current challenge of n-3 LC PUFA dietary shortage for fish health, aquaculture production and nutritional security of human population, and identifies knowledge gaps that must be addressed to ensure both ecological resilience and sustainable aquaculture development in a rapidly changing world.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 4-18"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088344","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}
Phototropin, a blue-light sensing serine/threonine kinase, plays a pivotal role in regulating diverse photophysiological processes in both plants and algae. In Chlamydomonas reinhardtii, phototropin (CrPhot) localizes to the eyespot and flagella, coordinating key cellular functions such as phototaxis, photosynthesis, gametogenesis, and chlorophyll biosynthesis. Although prior studies have identified phototropin interactions with signaling proteins such as channelrhodopsins and light-harvesting complex proteins, its broader interaction network and regulatory mechanisms remain poorly understood. In this study, we identified novel protein partners of phototropin and their roles in modulating its regulatory functions in C. reinhardtii. Employing a range of intraflagellar transport (IFT) mutants of C. reinhardtii, we demonstrated that phototropin localization to the flagella and eyespot is IFT-mediated. Our results reveal novel interactions between phototropin and other photoreceptors, including-channelrhodopsins (ChR1 and ChR2), chlamyopsin 6, LOV-histidine kinases (LOV-HK1, LOV-HK2) and the signaling protein- 14-3-3. CRISPR-Cas9 generated knockouts of phototropin led to reduced expression of ChR1 and 14-3-3, accompanied by impaired photomotility of the mutants. Additionally, gene expression of LOV-HK1 and LOV-HK2 were found to be elevated under UV-light in C. reinhardtii and these had altered expression in phototropin knockout line. These findings provide novel insights into phototropin interactome and elucidate molecular mechanisms underlying its localization and signaling functions in C. reinhardtii. This work advances our understanding of phototropin-mediated signal transduction and lays the groundwork for future exploration of its broader physiological roles in cellular responses.
{"title":"Phototropin localization and interactions regulate photophysiological processes in Chlamydomonas reinhardtii","authors":"Sunita Sharma , Kumari Sushmita , Rajani Singh , Sibaji K. Sanyal , Suneel Kateriya","doi":"10.1016/j.biochi.2025.08.014","DOIUrl":"10.1016/j.biochi.2025.08.014","url":null,"abstract":"<div><div>Phototropin, a blue-light sensing serine/threonine kinase, plays a pivotal role in regulating diverse photophysiological processes in both plants and algae. In <em>Chlamydomonas reinhardtii</em>, phototropin (CrPhot) localizes to the eyespot and flagella, coordinating key cellular functions such as phototaxis, photosynthesis, gametogenesis, and chlorophyll biosynthesis. Although prior studies have identified phototropin interactions with signaling proteins such as channelrhodopsins and light-harvesting complex proteins, its broader interaction network and regulatory mechanisms remain poorly understood. In this study, we identified novel protein partners of phototropin and their roles in modulating its regulatory functions in <em>C. reinhardtii</em>. Employing a range of intraflagellar transport (IFT) mutants of <em>C. reinhardtii</em>, we demonstrated that phototropin localization to the flagella and eyespot is IFT-mediated. Our results reveal novel interactions between phototropin and other photoreceptors, including-channelrhodopsins (ChR1 and ChR2), chlamyopsin 6, LOV-histidine kinases (LOV-HK1, LOV-HK2) and the signaling protein- 14-3-3. CRISPR-Cas9 generated knockouts of <em>phototropin</em> led to reduced expression of <em>ChR1</em> and <em>14-3-3</em>, accompanied by impaired photomotility of the mutants. Additionally, gene expression of <em>LOV-HK1</em> and <em>LOV-HK2</em> were found to be elevated under UV-light in <em>C. reinhardtii</em> and these had altered expression in <em>phototropin</em> knockout line. These findings provide novel insights into phototropin interactome and elucidate molecular mechanisms underlying its localization and signaling functions in <em>C. reinhardtii</em>. This work advances our understanding of phototropin-mediated signal transduction and lays the groundwork for future exploration of its broader physiological roles in cellular responses.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 150-162"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877237","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 : 2025-12-01Epub Date: 2025-08-09DOI: 10.1016/j.biochi.2025.08.013
Isabele G. Frasson-Uemura , Franciele P. Dall’Aqua , Lunna U. Bosquetti , Otávio Vinícius C. Jorge , Thais T. Braga , Maria F. Siqueira , Manoel O.E. Favaro , Vania G.M. Mattaraia , Rui Curi , Roberto B. Bazotte , Priscila Cassolla , Gisele Lopes Bertolini
Liver glycogen catabolism was investigated in young adult Goto-Kakizaki rats (GK group) and compared with non-diabetic Wistar rats (Control group). The diabetic condition of GK rats was confirmed by hyperglycemia and insulin resistance. Glycogen catabolism was intensified during the infusion of epinephrine (10 μM, 20 μM, and 40 μM), phenylephrine (2 μM, 4 μM, and 6 μM), and glucagon (1 nM) in both Control and GK livers. The degree of glycogen catabolism during these infusions was similar in Control and GK rats, despite the higher liver glycogen content observed in the GK rats. However, a diminished intensification of hepatic glucose production was observed in GK rats during the infusion of isoproterenol (10 μM, 20 μM, and 40 μM). To further investigate this difference, the effect of cAMP, the intracellular mediator of isoproterenol, on liver glycogen catabolism was examined. Livers from GK rats showed no response to 3 μM and 5 μM cAMP but displayed a similar intensification of glycogen catabolism at 7 μM and 9 μM cAMP as the Control group. Interestingly, a higher intensification of glycogen catabolism was observed in GK livers during the infusion of 3 μM dibutyryl-cAMP, a phosphodiesterase-resistant cAMP analog, suggesting that cAMP inactivation by phosphodiesterases might be increased in GK livers. While these findings suggest a possible involvement of phosphodiesterases in the reduced response to isoproterenol, the evidence is insufficient to conclusively establish this mechanism. It can be concluded that liver glycogenolysis does not contribute to the hyperglycemia and glucose intolerance observed in young adult GK rats and that cAMP-mediated intracellular signaling appears to be attenuated in the livers of these animals.
{"title":"Liver glycogen catabolism in young adult Goto-Kakizaki rats","authors":"Isabele G. Frasson-Uemura , Franciele P. Dall’Aqua , Lunna U. Bosquetti , Otávio Vinícius C. Jorge , Thais T. Braga , Maria F. Siqueira , Manoel O.E. Favaro , Vania G.M. Mattaraia , Rui Curi , Roberto B. Bazotte , Priscila Cassolla , Gisele Lopes Bertolini","doi":"10.1016/j.biochi.2025.08.013","DOIUrl":"10.1016/j.biochi.2025.08.013","url":null,"abstract":"<div><div>Liver glycogen catabolism was investigated in young adult Goto-Kakizaki rats (GK group) and compared with non-diabetic Wistar rats (Control group). The diabetic condition of GK rats was confirmed by hyperglycemia and insulin resistance. Glycogen catabolism was intensified during the infusion of epinephrine (10 μM, 20 μM, and 40 μM), phenylephrine (2 μM, 4 μM, and 6 μM), and glucagon (1 nM) in both Control and GK livers. The degree of glycogen catabolism during these infusions was similar in Control and GK rats, despite the higher liver glycogen content observed in the GK rats. However, a diminished intensification of hepatic glucose production was observed in GK rats during the infusion of isoproterenol (10 μM, 20 μM, and 40 μM). To further investigate this difference, the effect of cAMP, the intracellular mediator of isoproterenol, on liver glycogen catabolism was examined. Livers from GK rats showed no response to 3 μM and 5 μM cAMP but displayed a similar intensification of glycogen catabolism at 7 μM and 9 μM cAMP as the Control group. Interestingly, a higher intensification of glycogen catabolism was observed in GK livers during the infusion of 3 μM dibutyryl-cAMP, a phosphodiesterase-resistant cAMP analog, suggesting that cAMP inactivation by phosphodiesterases might be increased in GK livers. While these findings suggest a possible involvement of phosphodiesterases in the reduced response to isoproterenol, the evidence is insufficient to conclusively establish this mechanism. It can be concluded that liver glycogenolysis does not contribute to the hyperglycemia and glucose intolerance observed in young adult GK rats and that cAMP-mediated intracellular signaling appears to be attenuated in the livers of these animals.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 139-149"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823415","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 : 2025-12-01Epub Date: 2025-09-20DOI: 10.1016/j.biochi.2025.09.001
Priscilla Augusta de Sousa Fernandes , Rodrigo Santos Aquino de Araújo , Gabriel Gonçalves Alencar , Sheila Alves Gonçalves , Gildênia Alves de Araújo , Ewerton Yago de Sousa Rodrigues , Daniel Sampaio Alves , Ray Silva de Almeida , Cícera Datiane de Morais Oliveira-Tintino , Maria Gabriella S. Sidrônio , Valnês S. Rodrigues , Emanuelly Karla Araújo Padilha , Edeildo Ferreira da Silva , Anuraj Nayarisseri , Teresinha Gonçalves da Silva , Henrique Douglas de Melo Coutinho , Francisco Jaime Bezerra Mendonça-Junior
In response to the growing threat of antibiotic resistance, this study aimed to identify novel compounds capable of modulating and/or even restoring antibiotic efficacy by inhibiting bacterial efflux pumps. Thirteen 2-aminothiophene (2-AT) derivatives were synthesized and tested against Staphylococcus aureus strains overexpressing NorA and MepA pumps, which confer resistance to fluoroquinolones. Although the 2-ATs displayed little inherent antibacterial activity, several—particularly compounds P4, P7, and P8—significantly potentiated the effects of norfloxacin, ciprofloxacin, and ethidium bromide (EtBr), reducing their Minimum Inhibitory Concentrations (MICs) by up to fourfold. P7 and P8, both 2-aminoselenophene bioisosteres, emerged as especially effective, demonstrating strong efflux pump inhibitory (EPI) activity and, for the first time, confirming their ability to inhibit MepA-mediated efflux in S. aureus. Cytotoxicity assays on VeroE6 and HepG2 cell lines confirmed the safety profile of selected compounds. EtBr accumulation assays and molecular dynamics simulations further supported the mechanism of action, confirming that these derivatives inhibit efflux activity. Overall, the results highlight the potential of 2-AT derivatives—especially P7 and P8—as promising EPIs to combat fluoroquinolone-resistant S. aureus.
{"title":"2-Aminothiophene derivatives reduce resistance to fluoroquinolones in Staphylococcus aureus strains which overexpress NorA and MepA efflux pumps","authors":"Priscilla Augusta de Sousa Fernandes , Rodrigo Santos Aquino de Araújo , Gabriel Gonçalves Alencar , Sheila Alves Gonçalves , Gildênia Alves de Araújo , Ewerton Yago de Sousa Rodrigues , Daniel Sampaio Alves , Ray Silva de Almeida , Cícera Datiane de Morais Oliveira-Tintino , Maria Gabriella S. Sidrônio , Valnês S. Rodrigues , Emanuelly Karla Araújo Padilha , Edeildo Ferreira da Silva , Anuraj Nayarisseri , Teresinha Gonçalves da Silva , Henrique Douglas de Melo Coutinho , Francisco Jaime Bezerra Mendonça-Junior","doi":"10.1016/j.biochi.2025.09.001","DOIUrl":"10.1016/j.biochi.2025.09.001","url":null,"abstract":"<div><div>In response to the growing threat of antibiotic resistance, this study aimed to identify novel compounds capable of modulating and/or even restoring antibiotic efficacy by inhibiting bacterial efflux pumps. Thirteen 2-aminothiophene (2-AT) derivatives were synthesized and tested against <em>Staphylococcus aureus</em> strains overexpressing NorA and MepA pumps, which confer resistance to fluoroquinolones. Although the 2-ATs displayed little inherent antibacterial activity, several—particularly compounds <strong>P4</strong>, <strong>P7</strong>, and <strong>P8</strong>—significantly potentiated the effects of norfloxacin, ciprofloxacin, and ethidium bromide (EtBr), reducing their Minimum Inhibitory Concentrations (MICs) by up to fourfold. <strong>P7</strong> and <strong>P8</strong>, both 2-aminoselenophene bioisosteres, emerged as especially effective, demonstrating strong efflux pump inhibitory (EPI) activity and, for the first time, confirming their ability to inhibit MepA-mediated efflux in <em>S</em>. <em>aureus</em>. Cytotoxicity assays on VeroE6 and HepG2 cell lines confirmed the safety profile of selected compounds. EtBr accumulation assays and molecular dynamics simulations further supported the mechanism of action, confirming that these derivatives inhibit efflux activity. Overall, the results highlight the potential of 2-AT derivatives—especially <strong>P7</strong> and <strong>P8</strong>—as promising EPIs to combat fluoroquinolone-resistant <em>S. aureus</em>.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 191-206"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126201","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 : 2025-12-01Epub Date: 2025-09-08DOI: 10.1016/j.biochi.2025.09.002
Ting Kang , Ruizhe Huang , Ruiheng Wang , Han Liu , Siyu Chen
The nuclear factor of activated T cells 3 (NFATc3) plays a significant role in various cancer-related processes, but its interactions with transcriptional modulators, particularly Promyelocytic Leukemia protein (PML), remain poorly understood. PML, a nuclear scaffold protein, is involved in tumor suppression and transcriptional regulation. This study investigates the interaction between NFATc3 and PML, focusing on the role of SUMOylation and its impact on downstream target genes. In vitro experiments, including mass spectrometry and Co-immunoprecipitation (Co-IP), were conducted to explore this interaction. Additionally, constructs with lysine-to-arginine (K→R) mutations at key SUMOylation sites were generated to determine whether PML SUMOylation is necessary for its interaction with NFATc3. We also assessed the impact of NFATc3 SUMOylation on its binding to PML. Chromatin immunoprecipitation (ChIP) and quantitative real-time PCR (qRT-PCR) were employed to measure the expression of downstream genes (Lgr5 and Olfm4) under NFATc3 and PML overexpression or knockdown conditions. Pharmacological treatment with arsenic sulfide (As4S4) was used to further investigate modulation of the PML-NFATc3 axis. Our findings revealed that the NFATc3-PML interaction is independent of the SUMOylation status of PML. Additionally, mutations in NFATc3 SUMOylation sites did not affect its binding to PML. The PML-NFATc3 axis regulates Lgr5 and Olfm4 expression, and co-expression of NFATc3 and PML synergistically upregulated these genes. Arsenic sulfide treatment reduced this synergistic effect, indicating its potential as a modulator. This study provides new insights into the regulatory mechanisms of NFATc3 and PML, suggesting potential therapeutic targets in cancer.
{"title":"NFATc3 and PML synergistically regulate tumor-associated gene expression in a SUMOylation-Independent manner","authors":"Ting Kang , Ruizhe Huang , Ruiheng Wang , Han Liu , Siyu Chen","doi":"10.1016/j.biochi.2025.09.002","DOIUrl":"10.1016/j.biochi.2025.09.002","url":null,"abstract":"<div><div>The nuclear factor of activated T cells 3 (NFATc3) plays a significant role in various cancer-related processes, but its interactions with transcriptional modulators, particularly Promyelocytic Leukemia protein (PML), remain poorly understood. PML, a nuclear scaffold protein, is involved in tumor suppression and transcriptional regulation. This study investigates the interaction between NFATc3 and PML, focusing on the role of SUMOylation and its impact on downstream target genes. In vitro experiments, including mass spectrometry and Co-immunoprecipitation (Co-IP), were conducted to explore this interaction. Additionally, constructs with lysine-to-arginine (K→R) mutations at key SUMOylation sites were generated to determine whether PML SUMOylation is necessary for its interaction with NFATc3. We also assessed the impact of NFATc3 SUMOylation on its binding to PML. Chromatin immunoprecipitation (ChIP) and quantitative real-time PCR (qRT-PCR) were employed to measure the expression of downstream genes (Lgr5 and Olfm4) under NFATc3 and PML overexpression or knockdown conditions. Pharmacological treatment with arsenic sulfide (As<sub>4</sub>S<sub>4</sub>) was used to further investigate modulation of the PML-NFATc3 axis. Our findings revealed that the NFATc3-PML interaction is independent of the SUMOylation status of PML. Additionally, mutations in NFATc3 SUMOylation sites did not affect its binding to PML. The PML-NFATc3 axis regulates Lgr5 and Olfm4 expression, and co-expression of NFATc3 and PML synergistically upregulated these genes. Arsenic sulfide treatment reduced this synergistic effect, indicating its potential as a modulator. This study provides new insights into the regulatory mechanisms of NFATc3 and PML, suggesting potential therapeutic targets in cancer.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 207-217"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034798","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 : 2025-12-01Epub Date: 2025-08-30DOI: 10.1016/j.biochi.2025.08.018
Wenbo Cao, Jun Tan
Comprehensive characterization of fatty acid (FA) structures has important value, as they are important components of cells and are crucial for cell structure and function. However, in view of the different structural possibilities of unsaturated FAs due to the carbon–carbon double bond (CC) location and its chemical configuration, there are still certain difficulties in characterizing unsaturated FAs with high structural specificity. In this work, we present a method based on nuclear magnetic resonance (NMR) spectroscopy for comprehensive characterization of unsaturated FAs. Combining 1D and 2D-NMR spectroscopy, it could provide diagnostic information specific to CC locations and stereochemistry of unsaturated FAs, facilitating FA isomers identification. Structural characterization of unsaturated FAs at the isomeric level has been validated by examination of multiple sample types through our proposed approach. The capability of the proposed method for relative quantitation of FA isomers utilizing its specific diagnostic peaks was also demonstrated. Unlike conventional approaches requiring both reference standards and extensive sample processing, the current proposed method represents a potential alternative by resolving unsaturated lipid structures at high structural level directly.
{"title":"Characterization of unsaturated fatty acids with high structural specificity by nuclear magnetic resonance spectroscopy","authors":"Wenbo Cao, Jun Tan","doi":"10.1016/j.biochi.2025.08.018","DOIUrl":"10.1016/j.biochi.2025.08.018","url":null,"abstract":"<div><div>Comprehensive characterization of fatty acid (FA) structures has important value, as they are important components of cells and are crucial for cell structure and function. However, in view of the different structural possibilities of unsaturated FAs due to the carbon–carbon double bond (C<img>C) location and its chemical configuration, there are still certain difficulties in characterizing unsaturated FAs with high structural specificity. In this work, we present a method based on nuclear magnetic resonance (NMR) spectroscopy for comprehensive characterization of unsaturated FAs. Combining 1D and 2D-NMR spectroscopy, it could provide diagnostic information specific to C<img>C locations and stereochemistry of unsaturated FAs, facilitating FA isomers identification. Structural characterization of unsaturated FAs at the isomeric level has been validated by examination of multiple sample types through our proposed approach. The capability of the proposed method for relative quantitation of FA isomers utilizing its specific diagnostic peaks was also demonstrated. Unlike conventional approaches requiring both reference standards and extensive sample processing, the current proposed method represents a potential alternative by resolving unsaturated lipid structures at high structural level directly.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 177-190"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982282","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 : 2025-12-01Epub Date: 2025-10-06DOI: 10.1016/j.biochi.2025.10.001
Aditi Pathak , Ramanathan Sowdhamini
Gap junctions are multimeric intercellular channels that permit ions and small molecules to pass directly from one cell to another. Despite being fundamental to multicellular life, these channels are formed by distantly related protein families: innexins in invertebrates and connexins in vertebrates. Vertebrates also express pannexins, distant homologs of primordial innexins, which only form hemichannels. While these families have diverse sequences and different oligomeric states, their monomeric structures are highly similar. We generated structure-guided sequence alignments to establish equivalent residues across innexins, connexins, and pannexins. Further, computational approaches for determining protein-protein interaction hotspots, residue conservation, accessible surface area and local conformations of residues, provide insights into the relationships between residue positions and channel properties. We find that exposed transmembrane residues of TM1 and TM2 are more conserved than those in TM3 and TM4, especially in connexins and pannexins. Moreover, we see that residues in the extracellular extended hairpins of pannexins show more conformational flexibility, in variable protein blocks, than equivalent residues in connexins. This hints that the rigidity of this element could be a prerequisite for hemichannel docking. Finally, we identify inter- and intra-hemichannel interface hotspots that are positionally conserved across the families, implying their role in hemichannel and, ultimately, gap junction formation. Such analyses reveal a molecular grammar that underlies gap junction design and offer a basis for targeted perturbation of channel properties.
{"title":"Computational structural analysis sheds light on the molecular grammar of gap junction proteins","authors":"Aditi Pathak , Ramanathan Sowdhamini","doi":"10.1016/j.biochi.2025.10.001","DOIUrl":"10.1016/j.biochi.2025.10.001","url":null,"abstract":"<div><div>Gap junctions are multimeric intercellular channels that permit ions and small molecules to pass directly from one cell to another. Despite being fundamental to multicellular life, these channels are formed by distantly related protein families: innexins in invertebrates and connexins in vertebrates. Vertebrates also express pannexins, distant homologs of primordial innexins, which only form hemichannels. While these families have diverse sequences and different oligomeric states, their monomeric structures are highly similar. We generated structure-guided sequence alignments to establish equivalent residues across innexins, connexins, and pannexins. Further, computational approaches for determining protein-protein interaction hotspots, residue conservation, accessible surface area and local conformations of residues, provide insights into the relationships between residue positions and channel properties. We find that exposed transmembrane residues of TM1 and TM2 are more conserved than those in TM3 and TM4, especially in connexins and pannexins. Moreover, we see that residues in the extracellular extended hairpins of pannexins show more conformational flexibility, in variable protein blocks, than equivalent residues in connexins. This hints that the rigidity of this element could be a prerequisite for hemichannel docking. Finally, we identify inter- and intra-hemichannel interface hotspots that are positionally conserved across the families, implying their role in hemichannel and, ultimately, gap junction formation. Such analyses reveal a molecular grammar that underlies gap junction design and offer a basis for targeted perturbation of channel properties.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 82-96"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254148","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 : 2025-12-01Epub Date: 2025-10-10DOI: 10.1016/j.biochi.2025.10.006
Maëlle Zonnequin , Marine Vallet , Ludovic Delage , Georg Pohnert , Catherine Leblanc , Gabriel V. Markov
Algae are photosynthetic organisms, responsible for the primary production in oceans and lakes. Brown algae have evolved independently from other major eukaryotic lineages, such as the Opistokonts (animals, fungi) or Archaeplastida (land plants, green and red algae). Within this lineage, there is considerable variation between species, which differ in ecology, diversity, and evolutionary features, suggesting specific adaptations in their changing marine environment. In this context, several questions remain regarding the evolution of brown algal metabolism, particularly in response to oxidative stress. This study explored the consequences of copper stress on two brown algae from the Ectocarpales order: the free-living Ectocarpus sp7 and the endophytic Laminarionema elsbetiae. Using PAM-based fluorescence measurements, we revealed that high copper exposure reduces the photosynthetic capacity and activity of the endophyte. Through a cutting-edge untargeted metabolomic approach using UHPLC-HRMS profiling, we detected metabolic alterations induced by short-term exposure to moderate copper concentration in both free-living and endophytic Ectocarpales. The metabolite-regulated response appears to be substantial in Ectocarpus sp7 compared to L. elsbetiae, as a greater number of up- and down-regulated features were detected. Among the discriminant ions identified by tandem mass spectrometry, our results confirmed that copper exposure triggers the metabolism of algal defense signaling, primarily through the upregulation of oxylipins, but mainly in Ectocarpus sp 7. Altogether, our findings suggest that in Ectocarpales, fine metabolic adaptation may have altered the metabolism linked to defense signaling, such as the oxylipin pathway, particularly in ecological niches like endophytic life.
{"title":"Differential impact of copper stress in two Ectocarpales: metabolic disruption and defensive signaling in the free-living Ectocarpus sp7 and the endophytic Laminarionema elsbetiae","authors":"Maëlle Zonnequin , Marine Vallet , Ludovic Delage , Georg Pohnert , Catherine Leblanc , Gabriel V. Markov","doi":"10.1016/j.biochi.2025.10.006","DOIUrl":"10.1016/j.biochi.2025.10.006","url":null,"abstract":"<div><div>Algae are photosynthetic organisms, responsible for the primary production in oceans and lakes. Brown algae have evolved independently from other major eukaryotic lineages, such as the Opistokonts (animals, fungi) or Archaeplastida (land plants, green and red algae). Within this lineage, there is considerable variation between species, which differ in ecology, diversity, and evolutionary features, suggesting specific adaptations in their changing marine environment. In this context, several questions remain regarding the evolution of brown algal metabolism, particularly in response to oxidative stress. This study explored the consequences of copper stress on two brown algae from the <em>Ectocarpales</em> order: the free-living <em>Ectocarpus</em> sp<em>7</em> and the endophytic <em>Laminarionema elsbetiae</em>. Using PAM-based fluorescence measurements, we revealed that high copper exposure reduces the photosynthetic capacity and activity of the endophyte. Through a cutting-edge untargeted metabolomic approach using UHPLC-HRMS profiling, we detected metabolic alterations induced by short-term exposure to moderate copper concentration in both free-living and endophytic <em>Ectocarpales</em>. The metabolite-regulated response appears to be substantial in <em>Ectocarpus</em> sp<em>7</em> compared to <em>L. elsbetiae</em>, as a greater number of up- and down-regulated features were detected. Among the discriminant ions identified by tandem mass spectrometry, our results confirmed that copper exposure triggers the metabolism of algal defense signaling, primarily through the upregulation of oxylipins, but mainly in <em>Ectocarpus</em> sp 7<em>.</em> Altogether, our findings suggest that in Ectocarpales, fine metabolic adaptation may have altered the metabolism linked to defense signaling, such as the oxylipin pathway, particularly in ecological niches like endophytic life.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"239 ","pages":"Pages 93-102"},"PeriodicalIF":3.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282121","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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