Biochimie最新文献

{"title":"Organelle localization and trafficking of ether lipids: Current evidence and open questions.","authors":"Denise Kummer, Katrin Watschinger","doi":"10.1016/j.biochi.2026.10.004","DOIUrl":"10.1016/j.biochi.2026.10.004","url":null,"abstract":"<p><p>Ether glycerophospholipids are abundant and functionally versatile membrane lipids whose defining sn-1 ether (plasmanyl), or vinyl ether (plasmenyl, plasmalogen) linkage, and polyunsaturated sn-2 chains provide membranes with unique biophysical and signaling properties. Biogenesis is partitioned between two organelles: peroxisomes establish the sn-1 ether linkage and deliver 1-O-alkyl intermediates to the endoplasmic reticulum, where headgroup addition and remodeling occur. Introduction of the vinyl ether double bond by plasmanylethanolamine desaturase then yields plasmalogens. Emerging evidence indicates that ether lipids are unevenly distributed across cellular membranes, reflecting both local metabolic control and selective trafficking. Biosynthetic intermediates are delivered from peroxisomes to the endoplasmic reticulum via ACBD4/5-VAPA/B membrane contact sites, which also couple ether lipid-flux to cholesterol homeostasis. At the plasma membrane, ATP8B2 flippase enforces inner leaflet enrichment of plasmalogens, linking their molecular shape to membrane curvature, raft organization, and signaling. Beyond these core sites, additional pools of ether lipids are detected in the Golgi, mitochondria, endolysosomal system, lipid droplets, and the nucleus, where they are proposed to support membrane organization, and trafficking, yet their organelle-specific functions and transport mechanisms remain poorly defined. In this review we summarize the current knowledge about cellular and subcellular distribution of ether lipids, their biosynthesis, remodeling, degradation, and intracellular trafficking. We also highlight recent methodological advances enabling organelle-resolved lipidomics and live-cell tracking of ether lipids and outline open questions regarding contact-site identity and regulation, transport specificity between plasmanyl and plasmenyl species, and pathophysiological mislocalization mechanisms.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing phospholipid bilayer structure and interaction using ATR-FTIR spectroscopy.","authors":"Merve Örer, Thomas Bürgi","doi":"10.1016/j.biochi.2026.10.013","DOIUrl":"10.1016/j.biochi.2026.10.013","url":null,"abstract":"<p><p>The cell membrane plays a critical role in maintaining cellular integrity and regulating interactions between the cell and its environment. The understanding of many biological processes relies on obtaining molecular level information on the structure and dynamic behaviour of membranes, interactions between molecules within the membrane, as well as interactions between membrane and external compounds. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy has emerged as a powerful analytical technique for investigating biological membranes due to its surface sensitivity and minimal sample preparation requirements. The technique enables the characterization of lipid bilayers, protein secondary structures, and membrane interactions with external molecules such as drugs or antimicrobial peptides. This mini-review summarizes the principles of ATR spectroscopy and highlights its applications in the study of lipid bilayers, including lipid organization, protein-lipid interactions, and membrane structural changes. The advantages, limitations, and future perspectives of ATR-based approaches in membrane research are also discussed.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphine-induced human erythrocyte cholinesterase inhibition is reactivable by oximes: A step towards antidote development for phosphine.","authors":"Deepak Yadav, Deepak Kumar, Sheemona Chowdhary, Rajasri Bhattacharyya, Dibyajyoti Banerjee","doi":"10.1016/j.biochi.2026.10.015","DOIUrl":"10.1016/j.biochi.2026.10.015","url":null,"abstract":"<p><p>Phosphine-releasing metal phosphides are used to protect stored grains. Phosphine gas can be fatal if inhaled. However, the easy availability of metal phosphides (like Aluminium phosphide) causes increased misuse to commit suicide. Phosphine is a mitochondrial poison and affects the body's major organs. Phosphine poisoning has no specific diagnostic biomarker or remedy/antidote. It is reported that phosphine inhibits erythrocyte cholinesterase activity. However, contradictory views regarding this issue exist, and no consensus has been reached yet. Further, it is completely unknown that even if phosphine inhibits erythrocyte cholinesterase activity, such inhibition is reactivated by standard oxime reactivators akin to organophosphorus pesticide-induced enzyme inhibition. Keeping in mind that there is no antidote to phosphine exposure, it is important to solve the reactivation issue in the context of phosphine-induced enzyme inhibition. The in-silico (molecular docking and molecular dynamics simulation studies) and in-vitro (electrophoretic and spectroscopic) studies were carried out to understand the effect of phosphine exposure on erythrocyte cholinesterase activity. Besides the oximes used to understand the reactivation of the enzyme activity. From the results, it was discovered that phosphine inhibits human erythrocyte cholinesterase, akin to neostigmine and dichlorvos. Moreover, such inhibition is reactivated by oximes. It is concluded that erythrocyte cholinesterase activity holds significant promise as a biomarker for phosphine inhalation toxicity, and oximes may serve as a potential antidote.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purification and Characterization of BfPLA₂: Fraction containing Acidic Asp49 Phospholipase A₂ Isoforms Isolated from the Snake Bothrops fonsecai.","authors":"Mariana Leite Alves, Caroline Serino-Silva, Daniel Carvalho de Souza, Stéphane Claverol, Kathleen Fernandes Grego, Caroline Tokarski, Anita Mitico Tanaka-Azevedo","doi":"10.1016/j.biochi.2026.10.014","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.014","url":null,"abstract":"<p><p>Among the various proteins found in the venom of snakes belonging to the genus Bothrops, which is responsible for the highest number of snakebite accidents in Brazil, Phospholipase A₂ (PLA₂) is one of the most important components. The present study demonstrated the isolation of a fraction containing two Asp49 PLA₂ isoforms from the endemic southeastern Brazilian snake Bothrops fonsecai, named BfPLA₂. The isolation was achieved through two chromatographic techniques: RP-HPLC using a Teknokroma Europa Protein 300 C18 column, followed by anion-exchange chromatography using a HiTrap Q FF column. SDS-PAGE and two-dimensional electrophoresis revealed proteins with an approximate molecular mass of 15 kDa and an isoelectric point close to 5, indicating acidic PLA₂ isoforms. Mass spectrometry analysis and bioinformatic analysis identified two isoforms with high similarity to PLA₂s previously described in literature, corroborating the protein family of the isolated toxins. BfPLA₂ showed maximum activity at 60 °C and pH 8.5 (Mean: 223.89 U/min/mg). Cytotoxic activity against the HeLa cell line was demonstrated (IC₅₀: 26.21 μg/mL), as well as anticoagulant activity, prolonging coagulation time by 74.1% at the highest dose, and hemolytic activity (IC₅₀: 8.26 μg/mL). The characterization of proteins isolated from snake venoms may contribute to a deeper understanding of snakebite envenomation, especially regarding Bothrops fonsecai, whose venom remains poorly characterized.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digestive lipases as therapeutic targets in obesity: From Orlistat to next-generation inhibitors.","authors":"Sihem Snini, Jannet Kamoun, Emna Moujehed, Alexandre Noiriel, Ahmed Aloulou, Abdelkarim Abousalham","doi":"10.1016/j.biochi.2026.10.012","DOIUrl":"10.1016/j.biochi.2026.10.012","url":null,"abstract":"<p><p>Obesity remains a global pandemic and a major driver of metabolic diseases, with current pharmacotherapies often limited by modest efficacy, systemic side effects, high costs, and weight regain after cessation. Targeting dietary lipid digestion via the inhibition of gastrointestinal lipases offers a mechanistically rational and peripherally acting therapeutic strategy. This review provides an updated, quantitative overview of human gastrointestinal lipolysis, emphasizing the sequential and complementary roles of human gastric lipase and human pancreatic lipase in dietary triglyceride absorption. We critically analyze the clinical proof-of-concept provided by Orlistat, the only approved digestive lipase inhibitor, whose utility is constrained by limited efficacy, significant gastrointestinal intolerance, and rare but severe hepatotoxicity. While next-generation systemic therapies like GLP-1 receptor agonists show superior weight loss, their chronic administration and high cost underscore the need for safer, localized alternatives. We systematically review recent strategies for developing superior digestive lipase inhibitors, including structure-based drug design, in silico screening, and bioguided fractionation of natural products (e.g., flavonoid derivatives). Emphasis is placed on the critical design principles required for next-generation inhibitors, including strict luminal confinement, high selectivity for digestive lipases, and controlled, reversible inhibition to improve tolerability. By bridging biochemical insights with pharmacological challenges, this review outlines a roadmap for the development of safer, more effective lipid-targeted therapies to combat obesity.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine Aspergillus terreus produces a chitinase exhibiting a substrate specific mode of enzymatic action.","authors":"Sancharini Das, Debasis Roy, Ramkrishna Sen","doi":"10.1016/j.biochi.2026.10.010","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.010","url":null,"abstract":"<p><p>Marine Aspergillus terreus is explored as an important chitinase-producing fungal strain for N-Acetyl-D-Glucosamine (GlcNAc) production from chitin substrates. Here, a purified extracellular 45 kDa chitinase of marine Aspergillus terreus (accession number JQ248076) was characterized in terms of substrate specificity. Conventionally, endochitinase cleaves chitin randomly to produce GlcNAc and its various multimers. whereas, exochitinases cleave the chitin from its reducing end and produce either GlcNAc or chitobiose (GlcNAc dimer). In the present chitinase characterization, the HPLC followed by HRMS analyses revealed differential product formation from the chitin substrates of varied chain length. With swollen chitin , the enzyme produced GlcNAc as a predominant product; whereas with chitohexaose substrate, a mixture of GlcNAc and its oligomers was obtained. Although mass spectrometry-based proteomics analysis identified the isolated chitinase as an endochitinase 1 precursor (Accession XP_001217186). However, the enzyme kinetic study exhibited higher catalytic efficiency for exochitinase-specific dimeric chromogenic substrate in comparison to endochitinase-specific tetrameric fluorogenic substrate, which indicated predominantly exochitinase behaviour of the enzyme. Further, the in silico study predicted a differential cleavage pattern of the enzyme, which could be due to different mode of substrate binding and processive mechanism through the tunnel-shaped binding cleft of the enzyme. The substrate specificsubstrate specific mode of catalytic activity of present chitinase was further confirmed by a molecular docking study with different lengths of substrates. With unique substrate specific substrate specific mode of action, the chitinase of marine Aspergillus terreus offers a great promise for the production of GlcNAc.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfoquinovosyldiacylglycerol (SQDG) in chloroplast-poor tissues: What can lipidomics tell us?","authors":"Supakorn Potijun, Supaart Sirikantaramas, Hubert Schaller","doi":"10.1016/j.biochi.2026.10.011","DOIUrl":"10.1016/j.biochi.2026.10.011","url":null,"abstract":"<p><p>Sulfoquinovosyldiacylglycerol (SQDG) is an anionic sulfolipid of plastid membranes, classically associated with chloroplasts and thylakoids. Its detection by lipidomics in chloroplast-poor tissues raises a central problem: how can a reported SQDG signal be validated, and what evidence is required to determine its plastid context and biological meaning? In this critical narrative review, we reassess evidence beyond chloroplast-dominated tissues and evaluate both the strength of evidence for SQDG occurrence or function and the steps required to test lipidomics-derived hypotheses. The literature supports context-dependent rather than universal interpretations. Direct organelle-level lipid evidence from isolated non-green plastids remains limited; etioplast genetics supports an SQDG-related role in non-photosynthetic plastid membrane development; phosphate-deprived roots support phosphorus-economy remodeling; and sulfur-starvation studies establish regulated SQDG turnover and sulfur remobilization. By contrast, chromoplast and woody-tissue interpretations remain unresolved. These findings show that SQDG abundance alone is hypothesis-generating rather than diagnostic of function. We therefore propose a decision-tree framework that moves from chemical confirmation of the lipid signal to spatial localization, SQD1/SQD2-associated biosynthetic capacity, nutrient context, tissue-specific perturbation, and phenotype testing. This framework provides criteria for moving from lipidomic detection to supported biological interpretation in chloroplast-poor tissues.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Structural and Metabolic Reprogramming by Docosahexaenoic Acid in Neuronal Cell Models of Alzheimer's Disease\".","authors":"Awdi Rana, Plourde Mélanie, Lo Van Amanda, Bernoud-Hubac Nathalie","doi":"10.1016/j.biochi.2026.10.005","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.005","url":null,"abstract":"<p><p>Docosahexaenoic acid (DHA; 22:6n-3) is the most abundant omega-3 polyunsaturated fatty acid in the mammalian brain and an essential structural component of neuronal membranes. Several research studies indicate that DHA plays critical roles in maintaining membrane lipid composition, synaptic integrity, mitochondrial function, and metabolic homeostasis, processes that are disrupted in Alzheimer's disease (AD) and other neurodegenerative disorders. Because brain DHA availability depends largely on systemic metabolism and liver-brain communication, alterations in DHA homeostasis have been proposed as contributing factors to AD pathogenesis. In vitro neuronal culture models have been pivotal in investigating the molecular and biochemical mechanisms underlying DHA-mediated neuroprotection under disease-related conditions. This mini review summarizes how DHA treatment modulates cellular membrane organisation, synaptogenesis and cytoskeletal integrity, and its neuroprotective role in in vitro neuronal models of AD. Collectively, the literature supports DHA as a key modulator of the structure and metabolic mechanisms at the cellular level and supports the hypothesis that its greatest benefit may occur as a preventive or early-stage intervention. Although effective therapeutic interventions are still lacking, and more investigations integrating next-generation cellular models are still needed, these models provide crucial insights for developing targeted therapeutic applications in AD.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extending the lifespan of human mesenchymal stromal cells: Approaches to immortalization and clinical prospects.","authors":"S Gokul Krishna, Nikshitha Kulal, Suresh Kannan, Uday Kumar Kolkundkar, Abhishek Kumar Singh, Samatha Bhat, Raviraja N Seetharam","doi":"10.1016/j.biochi.2026.10.009","DOIUrl":"10.1016/j.biochi.2026.10.009","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have a limited proliferative lifespan associated with replicative senescence, although the extent and onset of replicative senescence may vary among MSC sources. The immortalization of MSCs is being investigated as a strategy to extend proliferative capacity and facilitate scale-up. Moreover, immortalization may reduce the need for repeated isolation and expansion of primary MSCs, potentially facilitating the generation of sufficient cell numbers for research and manufacturing. Standardizing efficient methodologies remains important for consistent GMP manufacturing, product stability, and clinical translation. This review focuses on diverse strategies employed over the past 10 years to generate immortal MSCs, including induced pluripotent stem cell (iPSC)-derived sources and MSC-derived approaches. To determine whether the generated immortalized MSCs are functionally equivalent to primary MSCs, current trends and studies in the R&D phase are briefly discussed. Furthermore, this review highlights the underreported baseline stability assays and the need for comprehensive stability validation in the R&D phase. Additionally, the therapeutic potential of immortal MSCs is discussed, with an emphasis on their prospective applications in cell-based therapies and outlining future directions for their development.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cells and their exosomes modulate sebocyte fate and lipid-associated proteomic-lipidomic remodeling.","authors":"Maryam Adelipour, Mohamed A Gab-Allah, Mingyu Kim, Sangsoo Lee, Kee K Kim, Ga Seul Lee, Jeong Hee Moon, David M Lubman, Jeongkwon Kim","doi":"10.1016/j.biochi.2026.10.003","DOIUrl":"10.1016/j.biochi.2026.10.003","url":null,"abstract":"<p><p>Sebocytes regulate skin lipid production and inflammatory homeostasis, yet how mesenchymal stem cells (MSCs) and MSCs-derived exosomes reshape sebocyte function remains unclear. This study compared the effects of indirect MSCs co-culture and MSCs-derived exosome treatment on MTS-associated metabolic activity, intracellular lipid droplet accumulation, proteomic remodeling, and lipidomic profiles in sebocytes. Human sebocytes were indirectly co-cultured with bone marrow-derived MSCs using transwell inserts or treated with MSCs-derived exosomes under proliferative or low-serum, lipid accumulation-promoting conditions. MTS-associated metabolic activity was assessed using the MTS assay, intracellular lipid droplet accumulation using Nile Red staining, proteomic remodeling using label-free LC-MS/MS, and lipidomic changes using untargeted LC-MS lipidomics. Indirect MSCs co-culture reduced MTS-associated metabolic activity, particularly under low-serum conditions, while markedly increasing intracellular lipid droplet accumulation. Proteomic analysis indicated that MSCs co-culture promoted cytoskeletal, adhesion-related, and lipid-handling remodeling. Lipidomics further revealed broad lipid-class reprogramming, characterized by increased phospholipid-associated features and reduced lysophospholipid-associated features. In contrast, MSCs-derived exosomes increased MTS-associated metabolic activity under low-serum conditions, while intracellular lipid droplet accumulation remained largely comparable to control levels. Exosome treatment induced more selective proteomic changes related to proteostasis, mitochondrial adaptation, and vesicular trafficking/signaling, with limited lipidomic alterations that did not remain significant after FDR correction. MSCs co-culture and MSCs-derived exosomes exert biologically distinct effects on sebocytes. Whole MSCs co-culture drives extensive lipid-associated remodeling, whereas isolated exosomes mainly increase MTS-associated metabolic activity and induce adaptive proteomic responses, suggesting that exosomes transmit only part of the broader MSCs paracrine influence on sebocyte biology.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}