Biochimica et biophysica acta. General subjects最新文献

{"title":"Nitric oxide in plant stress: Rewilding and restoring signaling for enhancing plant growth and development","authors":"Sumreen Amin Shah ,&nbsp;Awdhesh Kumar Mishra ,&nbsp;Abdul Rehaman ,&nbsp;Sumit G. Gandhi ,&nbsp;Arif Tasleem Jan","doi":"10.1016/j.bbagen.2025.130837","DOIUrl":"10.1016/j.bbagen.2025.130837","url":null,"abstract":"<div><div>Plants, represented as a complex system, are continuously exposed to environmental conditions that affect their growth and development, and sometimes their survival. Being sessile, they complete their life cycle under the influence of varied environmental constraints (biotic and abiotic), that adversely affect the produce's quality and productivity. Plants have evolved several defense strategies orchestrated through phytohormones that play a pivotal role in conferring resistance to stress. Nitric oxide (NO), an endogenously produced gaseous hormone, has emerged as a saviour in plant's response to different stresses. It plays an active role in the growth and development of plants, from seed dormancy and germination to growth, differentiation, flowering, fruiting, and ripening, besides affecting key metabolic processes such as photosynthesis. Endogenous production of NO and its interaction with phytohormones across different signaling cascades helps in alleviating the cellular damage caused by free radicals during drought, salinity, and other stresses. It contributes to stress resilience by inducing the synthesis of stress hormones such as ethylene (ET), which help plants to withstand adverse environmental constraints by minimizing the damage caused by different stresses. Exogenous application of NO exerts protective effects against different stresses by breaking seed dormancy and modulating germination, enhancing acquisition of mineral nutrients, photosynthetic functioning, production of antioxidant enzymes capable of neutralizing free radicals, and maintaining membrane integrity. These multifaceted roles of NO underscore its significance in plant stress tolerance. The present study offers valuable insights into NO production methods, involvement in growth and development, and a mechanistic view of its role in alleviating different stresses. In the current scenario, continued research into NO signaling mechanisms and cross-talk with other pathways seems essential for harnessing its potential in developing crops with enhanced resilience to environmental challenges.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130837"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366653","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}

{"title":"USP33-mediated stabilization of c-Myc drives glycolytic reprogramming and promotes ovarian cancer progression","authors":"Dejia Chen ,&nbsp;Yue Zhao ,&nbsp;Xiaobo Zhang ,&nbsp;Xiaocheng Shi ,&nbsp;Yiming Liu ,&nbsp;Ge Lou","doi":"10.1016/j.bbagen.2025.130830","DOIUrl":"10.1016/j.bbagen.2025.130830","url":null,"abstract":"<div><div>Ovarian cancer (OC) is one of the most lethal gynecological malignancies, characterized by late-stage presentation, high recurrence rates, and a lack of effective early diagnostic markers. Recent evidence suggests that deubiquitinating enzymes (DUBs) play pivotal roles in tumor development and metabolic reprogramming. Here, we identify and characterize the function of the deubiquitinase USP33 in regulating c-Myc stability and glycolytic metabolism in OC. Through quantitative PCR (qPCR) and Western blot analyses, we show that USP33 is significantly upregulated in both OC tissues and cell lines compared to normal controls. Functional assays reveal that USP33 knockdown markedly inhibits cell proliferation, migration, and invasion while promoting apoptosis. Metabolically, USP33 silencing reduces glucose uptake, lactate production, and the extracellular acidification rate, consistent with downregulation of key glycolytic enzymes (LDHA, GLUT1, and PKM2). Mechanistically, co-immunoprecipitation and ubiquitination assays demonstrate that USP33 interacts with and deubiquitinates c-Myc at K48-linked chains, thereby stabilizing c-Myc protein levels and enhancing its transcriptional activity. Moreover, c-Myc overexpression rescues the inhibitory effects of USP33 knockdown on both glycolysis and malignant phenotypes. Clinically, high USP33 expression correlates with poor prognosis, suggesting that the USP33–c-Myc axis may serve as both a prognostic biomarker and a potential therapeutic target. Taken together, our findings highlight a critical role for USP33 in OC pathogenesis by mediating c-Myc-driven glycolytic reprogramming, and they provide new insights for developing targeted treatment strategies aimed at disrupting this pathway.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130830"},"PeriodicalIF":2.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324394","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}

{"title":"MYO9B deficiency promoted head and neck tumor progression through HIF1α/MYC/STAT2 signaling pathway.","authors":"Simin Gao, Xia Gao, Ning Wang, Yuping Xie, Yuedi Tang","doi":"10.1016/j.bbagen.2025.130834","DOIUrl":"https://doi.org/10.1016/j.bbagen.2025.130834","url":null,"abstract":"<p><strong>Background: </strong>Myosin, a protein family primarily involved in muscle contraction and cell movement, plays critical roles in various biological processes. Increasing evidence suggests its implication in tumor development and progression. However, the underlying mechanism remains poorly understood. Our study aimed to explore the role and molecular mechanism of myosin IXB (MYO9B) in head and neck squamous cell carcinoma (HNSC) development.</p><p><strong>Methods: </strong>Utilizing The Cancer Genome Atlas (TCGA) database (n = 24) and analyzing clinical HNSC tissues (n = 24), we investigated the correlation between myosin encoding genes and HNSC progression. Cell proliferation and migration were assessed using CCK8 and Transwell assays to elucidate the tumor suppressive role of MYO9B. Additionally, Western blotting and immunostaining were conducted to evaluate the activation of HIF1α/c-Myc/STAT2 signaling. A 3D Matrigel Primary tumor cell culture model was established to assess the cisplatin resistance of HNSC cells.</p><p><strong>Results: </strong>We found that MYO9B deficiency predicted poor prognosis in HNSC patients. In vitro, inhibiting MYO9B enhanced the proliferative and migratory characteristics of HNSC cell lines. Mechanistically, our study showed that MYO9B deficiency upregulated HIF1α signaling, leading to c-Myc upregulation, which induced stem-like phenotypes in cancer cells and HNSC progression. Furthermore, c-Myc upregulated downstream STAT2 signaling, contributing to cisplatin resistance in HNSC cells. Blocking STAT2 signaling improved cisplatin outcomes in primary MYO9B-high HNSC tissues from patients.</p><p><strong>Conclusion: </strong>Our study highlights the tumor suppressive role of MYO9B through HI1F1α/c-Myc/STAT2 in HNSC, suggesting its potential as a diagnostic indicator and therapeutic target for clinical intervention.</p>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"130834"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301037","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}

{"title":"The polyphenols phloretin and quercetin are potent horseradish peroxidase (HRP) inhibitors","authors":"Ben Faerman ,&nbsp;Olivia Chalifoux ,&nbsp;Marek Michalak ,&nbsp;Luis B. Agellon ,&nbsp;Ryan J. Mailloux","doi":"10.1016/j.bbagen.2025.130833","DOIUrl":"10.1016/j.bbagen.2025.130833","url":null,"abstract":"<div><div>The discovery of horseradish peroxidase (HRP) has been highly advantageous because its unique chemistry can be applied to diagnostic tools, including the detection of oxidative distress markers like hydrogen peroxide (H₂O₂) in various experimental systems. Here, we made the surprising and compelling finding that the flavonoids, phloretin and quercetin, which are usually described in the literature as potent antioxidants, strongly inhibit the activity of HRP. Using the amplex ultrared (AUR) assay, we discovered that phloretin at a concentration as low as 50 μM abolishes the detection of H₂O₂ production by isolated liver mitochondria oxidizing pyruvate and malate. Phloretin also nullified the detection of H₂O₂ produced by liver mitochondria oxidizing succinate or dihydroorotate. Moreover, phloretin at 100 μM completely abolished the direct detection of H₂O₂ by AUR and quenched the detection of purified xanthine oxidase (XO) activity, but did not interfere with dichlorodihydrofluorescein diacetate (H₂-DCFDA) or dihydroethidine (DHE) fluorescent assays. Dose response assays revealed quercetin is a more potent inhibitor for HRP when compared to phloretin. Indeed, quercetin abolished resorufin fluorescence in AUR assays in the nM range whereas phloretin had no effect when detecting H₂O₂ <em>in vitro</em> or when it is formed by isolated liver mitochondria or cultured Huh-7 hepatoma and Mia-PaCa2 cells. Collectively, our findings demonstrate phloretin and quercetin, and potentially other polyphenols, potently interfere with HRP-dependent assays, which have strong implications for designing experiments that interrogate the antioxidant potential of flavonoids. Our results also indicate phloretin and quercetin could be applied as controls for HRP reporter assays.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130833"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301038","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}

{"title":"Antibiotic-induced mitochondrial dysfunction: Exploring tissue-specific effects on HEI-OC1 cells and peripheral blood mononuclear cells","authors":"Tianshi Liu ,&nbsp;Imen Chamkha ,&nbsp;Eskil Elmér ,&nbsp;Fredrik Sjövall ,&nbsp;Johannes K. Ehinger","doi":"10.1016/j.bbagen.2025.130832","DOIUrl":"10.1016/j.bbagen.2025.130832","url":null,"abstract":"<div><div>Antibiotics are crucial in treating infectious diseases, particularly in intensive care unit patients, but they can lead to side effects such as ototoxicity. A mechanism for this is antibiotics targeting mitochondrial components in eucaryotic cells, due to their resemblance of those in bacteria. Here we investigate how five classes of antibiotics (carbapenems, fluoroquinolones, aminoglycosides, glycopeptides, and oxazolidinones) affect mitochondrial respiratory function, ATP levels, mitochondrial membrane potential and levels of reactive oxygen species in an inner-ear derived epithelial cell line (HEI-OC1) and human primary blood cells (PBMCs) at clinically relevant concentrations.</div><div>Mitochondrial respiration in intact HEI-OC1 cells was suppressed in response to the majority of the tested antibiotics. This effect was lost when the HEI-OC1 cells were permeabilized and substrate supply controlled. Further in these cells, ROS levels were increased and ATP levels reduced. In contrast, no measure of mitochondrial function of PBMCs was affected by any antibiotics at the same concentration. We show that HEI-OC1 cells are sensitive to a broad range of antibiotics, and that the mechanism of toxicity to mitochondrial respiration is upstream of the mitochondrial respiratory chain, with downstream effects on mitochondrial respiration, ATP levels and ROS levels.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130832"},"PeriodicalIF":2.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293186","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}

{"title":"Baicalein benefits amyotrophic lateral sclerosis via reduction of Intraneuronal misfolded protein","authors":"Chen-Hung Ting ,&nbsp;Shao-Ting Tai ,&nbsp;Hsiang-Yu Chang ,&nbsp;Po-Ya Huang ,&nbsp;Lo-Fan Cheng ,&nbsp;Hsing-Jung Lai ,&nbsp;Yih-Chih Kuo ,&nbsp;Chia-Hsin Kao ,&nbsp;I-Fan Wang ,&nbsp;Li-Kai Tsai","doi":"10.1016/j.bbagen.2025.130831","DOIUrl":"10.1016/j.bbagen.2025.130831","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by muscle weakness and atrophy, with limited treatment options. The accumulation of misfolded proteins, such as misfolded superoxide dismutase 1 (mSOD1), contributes significantly to neuronal degeneration in ALS. Therapies targeting misfolded proteins represent a promising strategy. Baicalein, a flavonoid compound with neuroprotective properties, has shown efficacy in clearing misfolded proteins and improving behaviors in rodent models of Alzheimer's and Parkinson's diseases. However, its effects in ALS remain largely unexplored. This study demonstrated that baicalein treatment reduced total and misfolded SOD1 protein levels in both soluble and insoluble fractions of a motor neuron cell line overexpressing mutant SOD1. Baicalein also reduced intracellular SOD1 aggregates in cultured motor neurons transfected with <em>SOD1/G93A</em>, preserving neurite length. In an ALS mouse model expressing the <em>SOD1/G93A</em> transgene, baicalein treatment decreased mSOD1 aggregation, increased spinal motor neuron density, and reduced neuromuscular junction denervation. Furthermore, baicalein partially improved motor behaviors, as assessed by the rotarod test. These findings highlight baicalein's potential as a therapeutic agent for ALS, targeting intraneuronal misfolded proteins to ameliorate pathological changes and preserve motor function.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130831"},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239565","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}

{"title":"Tryptophan enforced alg-iron oxide nanoconjugates: A potential evalution for synergistic cancer therapy","authors":"Amy Sarah Benjamin ,&nbsp;Sunita Nayak","doi":"10.1016/j.bbagen.2025.130829","DOIUrl":"10.1016/j.bbagen.2025.130829","url":null,"abstract":"<div><div>The contribution of magnetic nanoparticles towards the diagnosis and therapy of cancer has seen an upward graph for the past decade owing to their excellent superparamagnetic properties and contrast imaging. The surface functionalization of these iron oxide nanoparticles plays a pivotal role in the toxicity, circulation, and agglomeration parameters of clinical translation. Natural-source-based sodium alginate is a very profound biomaterial used in all areas of tissue engineering. This paper aims to study the properties of alginate-coated iron oxide nanoparticles conjugated to the aromatic amino acid tryptophan for cancer targeting. The investigation involves fabrication of the conjugated nano-system followed by analysis of the physico-chemical properties using XRD and FT-IR, evaluation of its magnetic property using VSM which shows a good superparamagnetic behaviour, along with an excellent thermal stability as shown by TGA analysis. The hyperthermia activity of these particles shows a very good specific absorption rate followed by the antioxidant property of the nano-conjugate, which shows potential scavenging activity. The biocompatibility of these nanoparticles was studied on NIH-3T3 cell lines, which showed no toxic effects, thus making the nano-conjugate an efficient cancer-targeting and therapeutic agent for future cancer nanomedicine.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130829"},"PeriodicalIF":2.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239564","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}

{"title":"Ferroptosis induction, androgen biosynthesis disruption and prostate cancer suppression by androgen and vitamin D combination","authors":"Bobae Park,&nbsp;Subash Khadka,&nbsp;Jungmi Ahn,&nbsp;Jacqueline Vaquiz,&nbsp;Okunola Igbekoyi,&nbsp;Chung S. Song,&nbsp;Bandana Chatterjee","doi":"10.1016/j.bbagen.2025.130828","DOIUrl":"10.1016/j.bbagen.2025.130828","url":null,"abstract":"<div><div>Prostate cancer regression by hormonal vitamin D₃(calcitriol) is clinically untenable despite its well-documented anticancer effects in experimental models, since supraphysiologic dosing of calcitriol required in clinical settings causes hypercalcemia and other toxicities. We show that subnanomolar/low-nanomolar calcitriol, while non-inhibitory on its own, inhibited CRPC cells upon co-treatment with androgen (5α-DHT) at a physiologic level, evident from G1/S cell cycle arrest, induction of p21/Cip1, blockade of clonal cell growth, retardation of proliferation, migration and invasion of cells <em>in vitro</em>, and xenograft growth suppression <em>in vivo</em>. AKR1D1, an androgen-inactivating 5β-reductase, was upregulated &gt;30-fold upon calcitriol/DHT co-treatment, while each hormone individually did not induce AKR1D1. In contrast, HSD3β1, a key enzyme for androgen biosynthesis, was upregulated &gt;12-fold by calcitriol, which was blocked by DHT co-treatment. Elevated AKR1D1 and reduced HSD3β1 would lower intracellular androgens and contribute to CRPC repression. Autophagy mediated ferroptosis (ferritinophagy) paralleled CRPC growth inhibition by the hormone combination –indicated by LC3B induction, ferritin reduction, and upregulation of mRNAs encoding NCOA4, ALOX-5 and PTGS2 which are core participants in ferroptosis. The combination treatment caused lipid peroxidation, evident from the fluorescence shift of C11-BODIPY(581/591)-labeled cells from red to green, and from elevated malondialdehyde. GPX4 - an antioxidant peroxidase and ferroptosis regulator – was downregulated. Bipolar androgen therapy employing supraphysiologic testosterone is under clinical evaluation for efficacy against treatment-resistant metastatic CRPC, although the high androgen dose raises safety concerns. Vitamin D and androgen administered concurrently at physiologic levels may offer a superior alternative for arresting CRPC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130828"},"PeriodicalIF":2.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186431","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}

{"title":"Plasma-activated medium disrupts intercellular barrier function in HaCaT cells by suppressing claudin-1 expression via clathrin-dependent endocytosis","authors":"Chika Miyamoto ,&nbsp;Yuta Yoshino ,&nbsp;Hiromasa Tanaka ,&nbsp;Hirokazu Hara ,&nbsp;Satoshi Endo ,&nbsp;Akira Ikari","doi":"10.1016/j.bbagen.2025.130826","DOIUrl":"10.1016/j.bbagen.2025.130826","url":null,"abstract":"<div><div>The skin plays a critical role in protecting against water loss from the inside and pathogen invasion from the outside. The expression levels and localization of claudin-1 (CLDN1) are responsible for the tight junction (TJ) barrier function in the epidermis. Nonthermal atmospheric pressure plasma (NTAPP) has recently received attention as a novel tool in life sciences, including dermatology. NTAPP application showed useful effects on the skin, including antimicrobial activity, wound healing promotion, and anticancer activity for melanoma. However, it remains unknown how NTAPP indirect irradiation affects skin cells. In this study, we used the human epidermal keratinocyte HaCaT cells to clarify the effect of NTAPP-irradiated medium (PAM) on the epidermal TJ barrier function. Treatment with 30 % of the medium irradiated no distance from NTAPP (PAM0) significantly decreased the expression levels of CLDN1 protein. PAM0 significantly decreased the localization of CLDN1 in the cell-cell contact area. After PAM0 treatment, further culture without PAM0 significantly restored the expression and localization of CLDN1 to the same level as in the control cells. The PAM0-induced changes in protein expression and localization of CLDN1 involve lysosome degradation via a clathrin-dependent endocytosis. Treatment with PAM0 decreases transepithelial electrical resistance and increases the intercellular permeability of low-molecular-weight compounds but not high-molecular-weight compounds. The present study shows that treatment with PAM0 weakens intercellular permeability by decreasing the TJ localization of CLDN1 protein in human epidermal keratinocytes. The technology using NTAPP may be useful to promote transdermal absorption of drugs that are difficult to permeate into the body.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130826"},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169831","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}

{"title":"Computational modelling of olfactory receptors","authors":"Chiemela S. Odoemelam,&nbsp;Volker Steuber,&nbsp;Michael Schmuker","doi":"10.1016/j.bbagen.2025.130825","DOIUrl":"10.1016/j.bbagen.2025.130825","url":null,"abstract":"<div><div>Olfactory receptors (ORs), the largest subfamily of G protein-coupled receptors, are essential for detecting and interpreting environmental odorants in animals. Understanding their function is crucial for deciphering olfactory perception and exploring emerging roles in non-olfactory systems. With the recent surge in available sequence data and AI-based structural predictions, computational modelling has become indispensable for investigating OR structure, ligand binding, and activation mechanisms. This review provides a comprehensive overview of computational approaches used in OR research, including homology modelling, molecular docking, molecular dynamics simulations, free energy calculations, pharmacophore modelling, virtual screening, and machine learning-based predictions. Both ligand-based and structure-based pharmacophore modelling are discussed in detail, highlighting their respective applications, strengths, and limitations. While structure-based approaches have gained prominence due to advances in receptor structure prediction tools like AlphaFold, ligand-based pharmacophore modelling remains valuable in scenarios where structural data are limited or uncertain. Case studies illustrate how these techniques have been applied to identify novel OR–ligand interactions, explore receptor dynamics, and support drug discovery. Collectively, these computational strategies offer powerful tools for decoding OR function, guiding experimental validation, and expanding our understanding of olfactory signalling in health and disease.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130825"},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169830","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}