{"title":"Preventive effect of siphonaxanthin, a carotenoid from green algae, against diabetic nephropathy and lipid metabolism insufficiency in skeletal muscle","authors":"Jiawen Zheng, Yuki Manabe, Tatsuya Sugawara","doi":"10.1016/j.bbalip.2025.159604","DOIUrl":"10.1016/j.bbalip.2025.159604","url":null,"abstract":"<div><div>Diabetic nephropathy is a complication of diabetes mellitus characterized by the gradual progression of renal insufficiency, resulting in renal failure. Approximately 15 % or more of patients with type 2 diabetes mellitus have diabetic nephropathy. Siphonaxanthin is a green algal carotenoid noted for its strong biological activities, including anti-obesity effects. In this study, we aimed to evaluate the preventive effects of siphonaxanthin on diabetic nephropathy using db/db mice as a type 2 diabetes mellitus and diabetic nephropathy model. Ingestion of AIN-93G containing 0.004 % w/w siphonaxanthin did not improve plasma creatinine and urine albumin levels but significantly mitigated renal morphological changes in diabetic mice. Moreover, siphonaxanthin restored the decreased mRNA expression of fatty acid β-oxidation-related proteins in the skeletal muscle. These results indicate that siphonaxanthin can potentially ameliorate type 2 diabetes mellitus-induced kidney damage and lipid metabolism insufficiency in skeletal muscle. This study provides a possible daily nutraceutical solution for treating diabetic nephropathy and lipid metabolic abnormalities.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159604"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chou Shen, Sepalika Bandara, Sanae S. Imanishi, Mahip Kalra, Yoshikazu Imanishi, Johannes von Lintig
{"title":"Unveiling BCO2 function in macular pigment metabolism: Mitochondrial processing and expression in the primate retina","authors":"Chou Shen, Sepalika Bandara, Sanae S. Imanishi, Mahip Kalra, Yoshikazu Imanishi, Johannes von Lintig","doi":"10.1016/j.bbalip.2025.159600","DOIUrl":"10.1016/j.bbalip.2025.159600","url":null,"abstract":"<div><div>BCO2 (β-carotene oxygenase 2) converts carotenoids into apocarotenoids by oxidative cleavage across double bonds and controls carotenoid homeostasis in vertebrate tissues. In this study, we examined BCO2's expression, localization, and activity in human cell lines and the retina. We generated peptide antibodies directed against primate BCO2 and validated their specificity using recombinant BCO1 (β-carotene oxygenase 1) and BCO2 proteins expressed in bacteria. The antibodies specifically detected human BCO2 by Western blot. In BCO2 expressing HepG2 cells, the antibodies recognized a 65 kDa mitochondrial protein that co-migrated with a recombinant truncated 522-amino-acid BCO2 variant, suggesting post-translational processing of the 579 amino acid long human BCO2 protein. Immunohistochemical analysis of macaque retina sections revealed BCO2 localization in the retinal pigment epithelium, photoreceptor inner segments, plexiform layer, and ganglion cell layer. Co-staining with COX IV indicated a mitochondrial localization of retinal BCO2 within photoreceptor inner segments. Western blot analysis of human donor retinas, separated into central and peripheral regions, identified higher BCO2 expression in the peripheral retina. Enzymatic activity assays demonstrated that BCO2 interacted with Aster proteins that transport carotenoids within cells. Our studies establish BCO2 as a mitochondrial protein expressed in the primate retina, where it likely plays a pivotal role in the metabolism of macular pigments and the maintenance of retinal health.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159600"},"PeriodicalIF":3.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne-Mari Mustonen , Petro Julkunen , Laura Säisänen , Lauri Karttunen , Amir Esrafilian , Jusa Reijonen , Sylvain Tollis , Reijo Käkelä , Sanna P. Sihvo , Nina Höglund , Tytti Niemelä , Anna Mykkänen , Jussi Mäki , Heikki Kröger , Jari Arokoski , Petteri Nieminen
{"title":"Pain and functional limitations in knee osteoarthritis are reflected in the fatty acid composition of plasma extracellular vesicles","authors":"Anne-Mari Mustonen , Petro Julkunen , Laura Säisänen , Lauri Karttunen , Amir Esrafilian , Jusa Reijonen , Sylvain Tollis , Reijo Käkelä , Sanna P. Sihvo , Nina Höglund , Tytti Niemelä , Anna Mykkänen , Jussi Mäki , Heikki Kröger , Jari Arokoski , Petteri Nieminen","doi":"10.1016/j.bbalip.2025.159602","DOIUrl":"10.1016/j.bbalip.2025.159602","url":null,"abstract":"<div><div>This study investigated relationships between fatty acid (FA) profiles of extracellular vesicles (EVs) and cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma was collected from controls (<em>n</em> = 10), end-stage KOA patients at baseline (<em>n</em> = 12) and at 3 and 12 months (<em>n</em> = 11 and 9) after joint replacement surgery, and from KOA synovial fluid (SF) at baseline (<em>n</em> = 10). EVs were isolated with the exoEasy Maxi Kit or size-exclusion chromatography, and EV FAs were analyzed with gas chromatography–mass spectrometry. Articular cartilage loss was determined by magnetic resonance imaging, and knee pain and function were assessed through questionnaires and physiatric and neuromuscular examinations. The associations of these data with EV FA proportions were tested with the univariate analysis of variance adjusted for age and body adiposity. Higher proportions of 16:1n-7, 18:1n-7, and total monounsaturated FAs in plasma EVs were associated with less severe KOA symptoms, while higher 24:1n-9, total saturated FAs, and ratios of arachidonic acid to long-chain n-3 polyunsaturated FAs (PUFAs) were linked to KOA pain, independent of age and body adiposity. In SF EVs, higher product/precursor ratios of n-6 PUFAs were associated with increased joint stiffness, and higher total dimethyl acetals were linked to physical disability. EV FAs emerged as significant indicators of knee pain and function. The results can be utilized to discover novel biomarkers for KOA and may have implications for targeted prevention and treatment of KOA symptoms by using EVs with a specific FA cargo.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159602"},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The influence of IMPDH activity on ciliogenesis and adipogenesis of 3T3-L1 cells while undergoing differentiation","authors":"Kolsoom Shahdadnejad, Razieh Yazdanparast","doi":"10.1016/j.bbalip.2025.159603","DOIUrl":"10.1016/j.bbalip.2025.159603","url":null,"abstract":"<div><div>The functional roles of primary cilia and inosine 5′-monophosphate dehydrogenase (IMPDH) are among the hot topics in today's adipogenesis research. Considering the reported interaction between IMPDH and ADP Ribosylation Factor-Like GTPase 13B (ARL13B), as a key ciliary protein, our study focused on this interaction during the ciliogenesis process while 3T3-L1 pre-adipocytes undergoing differentiation to lipid-accumulating adipocytes. Our results indicated that, in the early days of differentiation, when cilium length is long, IMPDH expression is high and its interaction with ARL13B is low. Conversely, in the last days of differentiation, the cilia length and IMPDH expression reduced while, the IMPDH/ARL13B interaction remains high relative to the initial days. In either of these two situations, IMPDH was not documented within the cilia. The extent of the interaction between IMPDH and ARL13B might account for the lack of co-localization of IMPDH and ARL13B within cilia during the process of differentiation. Although, inhibiting IMPDH in the early days of differentiation did not have a significant effect on cilia length, it did reduce adipogenesis by limiting mitotic clonal expansion through arresting cells in the G1/G0 phase. These findings provide the ground for further research to investigate the relationship between the IMPDH/ARL13B interaction and cilia length, which decline in obesity.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159603"},"PeriodicalIF":3.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What was the scientific context in which I wrote my 1975 \"inositol phospholipids and cell surface receptor function\" review?","authors":"Robert H Bob Michell","doi":"10.1016/j.bbalip.2025.159601","DOIUrl":"https://doi.org/10.1016/j.bbalip.2025.159601","url":null,"abstract":"<p><p>50 years on from my BBA review, I was delighted to hear that many of the current leaders of research across \"The Multiverse of Phosphoinositides\" are contributing to an authoritative collection of articles on the current state of that cosmology of cell functions - and that three other inositidonauts who were launched from Birmingham are assembling it. When the phosphoinositidase C signalling pathway emerged into the cell regulation limelight during the early 1980s it drew attention to a family of metabolically atypical membrane phospholipids that most biologists had been comfortably ignoring. Looking back, it is remarkable how many important clues were already loitering in the literature, waiting for us to start to make sense of them in the 1970s.</p>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":" ","pages":"159601"},"PeriodicalIF":3.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Siyi Zhang , Fangqin Nie , Youjie Zeng , Zhousheng Yang , Wenmin Song , Xin Yan , Zizhao Tang , Yangxia Fu , Ren Guo
{"title":"RGFP966 inhibits palmitic acid induced VSMCs phenotypic transition by targeting ATGL","authors":"Siyi Zhang , Fangqin Nie , Youjie Zeng , Zhousheng Yang , Wenmin Song , Xin Yan , Zizhao Tang , Yangxia Fu , Ren Guo","doi":"10.1016/j.bbalip.2025.159597","DOIUrl":"10.1016/j.bbalip.2025.159597","url":null,"abstract":"<div><h3>Background</h3><div>The phenotypic switch of vascular smooth muscle cells (VSMCs) underlies the pathology of many cardiovascular diseases. Histone deacetylase 3 (HDAC3) is reported to upregulate in several cardiovascular diseases. RGFP966 is a highly selective HDAC3 inhibitor. This study aimed to explore the effects of RGFP966 on the phenotypic switch of VSMCs.</div></div><div><h3>Method</h3><div>First, we conducted an analysis of HDAC3 expression utilizing pertinent Gene Expression Omnibus (GEO) datasets. Then CCK-8, Edu, and wound healing assays were used to explore the effects of RGFP966 on the proliferation and migration of VSMCs and potential mechanisms at the cellular level.</div></div><div><h3>Results</h3><div>Our results showed that palmitic acid (PA) induced the accumulation of lipid droplets in VSMCs, downregulated Adipose triglyceride lipase (ATGL), and increased VSMC viability and migration, which were significantly reversed by RGFP966. Additionally, siRNA targeting ATGL dramatically enhanced the VSMCs injury induced by PA. The autophagy inhibitor 3-Methyladenine (3-MA) partially reversed the decreased ATGL expression caused by PA. Furthermore, the p-mTOR/mTOR ratio decreased under PA induction and rebounded after administration of RGFP966.</div></div><div><h3>Conclusion</h3><div>RGFP966 has a protective effect against VSMCs phenotype transitions, potentially related to the regulation of ATGL.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159597"},"PeriodicalIF":3.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decoding the excited-state dynamics of carbonyl-containing carotenoids: Insights from the Ind series","authors":"Daisuke Kosumi , Toshiyuki Kusumoto , Hideki Hashimoto","doi":"10.1016/j.bbalip.2025.159598","DOIUrl":"10.1016/j.bbalip.2025.159598","url":null,"abstract":"<div><div>Carotenoids are naturally occurring pigments essential for both light-harvesting and photoprotection in photosynthetic processes. Among these, carbonyl-containing carotenoids exhibit distinctive excited state properties due to the presence of intramolecular charge transfer (ICT) in their excited states. In this study, we synthesized a novel family of carotenoid analogs with varying numbers of conjugated double bonds, denoted as the <em>Ind series</em>, and conducted femtosecond pump-probe spectroscopy on these molecules in both acetone and <em>n</em>-hexane. The objective was to elucidate how the excited-state dynamics depend on the conjugation length. The spectroscopic characterization of the <em>Ind series</em> revealed several unique features: the observation of stimulated emission from the <sup>1</sup>A<sub>g</sub><sup>−</sup>/ICT state, the emergence of the <sup>1</sup><em>n</em>π<sup>∗</sup> state, triplet state formation mediated by the <sup>1</sup><em>n</em>π<sup>∗</sup> state, and an anomalous solvent dependence of the <sup>1</sup>A<sub>g</sub><sup>−</sup>/ICT state lifetimes. The relationship between conjugation length and excited state dynamics, as well as the ICT character of the <em>Ind series</em>, are thoroughly discussed.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159598"},"PeriodicalIF":3.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Firas Warda, Jennifer Batch, Lauren Graham, Michael J. Haas, Arshag D. Mooradian
{"title":"D-allulose enhances lipid oxidation in HepG2 cells via peroxisome proliferator-activated receptor α (PPARα)","authors":"Firas Warda, Jennifer Batch, Lauren Graham, Michael J. Haas, Arshag D. Mooradian","doi":"10.1016/j.bbalip.2025.159599","DOIUrl":"10.1016/j.bbalip.2025.159599","url":null,"abstract":"<div><div>Lipid accumulation in hepatocytes in non-alcoholic steatohepatitis (NASH) is attributed partly to loss of insulin-responsiveness and/or an increased pro-inflammatory state. Since the rare sugar D-allulose has insulin mimetic and anti-inflammatory properties, its effects on lipid accumulation in liver-derived cells was tested. In HepG2 cells exposed to 200 μM oleic acid for 72 h, D-allulose treatment decreased intracellular lipid accumulation with an IC<sub>50</sub> = 0.45 ± 0.07 mM. A similar effect was observed in cells treated with 10 μM gemfibrozil. D-allulose and gemfibrozil treatment increased oleic acid β-oxidation. Both D-allulose and gemfibrozil increased peroxisome proliferator-activated receptor α (PPARα) expression (two-fold) relative to control cells, while retinoid X receptor was unchanged. D-allulose and gemfibrozil increased PPARα-dependent genes including those involved in fatty acid β-oxidation (acyl-coenzyme A oxidase 1, long-chain-fatty-acid-coenzyme A ligase 5, and carnitine palmitoyltransferase 1 A). D-allulose and gemfibrozil also increased PPARα reporter gene expression and phosphorylation (Serine 12) which were both inhibited by the mitogen-activated protein (MAP) kinase inhibitor PD098059. Other MAP kinase inhibitors, including SB203580, SP600125, and BIX10289 had no effect on reporter gene expression. Oleic acid treatment, but not D-allulose or gemfibrozil, decreased sterol response element binding protein 1 and sterol response element binding protein 2 expression relative to cells not exposed to oleic acid, while peroxisome proliferator-activated receptor γ expression did not change. These results indicate that D-alluose mimics gemfibrozil effects on lipid content in HepG2 cells by promoting fatty acid β-oxidation via PPARα.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159599"},"PeriodicalIF":3.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dantrolene is an HDL-associated paraoxonase-1 activator with immunosuppressive and atheroprotective properties","authors":"Anastasia-Georgia Dedemadi , Eirini Sevdali , Daphne Georgiadou , Eftaxia-Konstantina Valanti , Elpida Neofotistou-Themeli , Theodoros Chanis , Panagiota Goutakoli , Efstathia Thymiakou , Elias Drakos , Georgia Christopoulou , Stavros Bournazos , Pantelis Constantoulakis , Panayotis Verginis , Dimitris Kardassis , Efstratios Stratikos , Prodromos Sidiropoulos , Angeliki Chroni","doi":"10.1016/j.bbalip.2025.159596","DOIUrl":"10.1016/j.bbalip.2025.159596","url":null,"abstract":"<div><div>Human paraoxonase 1 (PON1), an enzyme bound to high-density lipoprotein (HDL), hydrolyzes oxidized lipids and contributes to HDL atheroprotective functions. Decreased serum paraoxonase and arylesterase activities of PON1 have been reported in patients at increased atherosclerosis risk, such as rheumatoid arthritis patients, and associated with arthritis severity and cardiovascular risk. Agents that can modulate PON1 activity and HDL-mediated effects have not been discovered. Aiming to discover chemical tools that enhance PON1 activity, we screened a library of marketed drugs (956 compounds) to identify small molecules that can increase HDL-associated PON1 activity. Screening was performed by a kinetic absorbance assay using human HDL as a source of PON1, and paraoxon and phenyl acetate as substrates to measure paraoxonase and arylesterase activities, respectively. Screening identified the drug dantrolene as a potential PON1 activator, which was confirmed by enzymatic kinetic assays using recombinant wild-type PON1, as well as the PON1[L55M] variant displaying decreased enzyme activity in humans. Furthermore, we used the collagen-induced arthritis (CIA) mouse model to examine the effect of dantrolene on HDL properties and arthritis <em>in vivo</em>. Administration of dantrolene in CIA mice increased paraoxonase and arylesterase activities of PON1, as well as the antioxidant capacity of HDL, and reduced arthritis severity by inhibition of naïve CD4<sup>+</sup> T cell differentiation to effector memory cells and generation of Th1 cells. Collectively, our <em>in vitro</em> and <em>in vivo</em> findings indicate using small molecules to enhance HDL-associated PON1 activity is a tractable approach that could lead to novel therapeutics targeting immune responses and atherosclerosis.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159596"},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ekaterina A. Butikova , Nikita V. Basov , Artem D. Rogachev , Evgeniy V. Gaisler , Vladimir A. Ivanisenko , Pavel S. Demenkov , Aelita-Luiza A. Makarova , Timofey V. Ivanisenko , Ivan A. Razumov , Daria A. Kolomeyets , Sergey V. Cheresiz , Olga I. Solovieva , Kirill P. Larionov , Yulia S. Sotnikova , Yuri V. Patrushev , Nikolay A. Kolchanov , Andrey G. Pokrovsky , Nikolay A. Vinokurov , Vladimir V. Kanygin , Vasiliy M. Popik , Oleg A. Shevchenko
{"title":"Metabolomic and gene networks approaches reveal the role of mitochondrial membrane proteins in response of human melanoma cells to THz radiation","authors":"Ekaterina A. Butikova , Nikita V. Basov , Artem D. Rogachev , Evgeniy V. Gaisler , Vladimir A. Ivanisenko , Pavel S. Demenkov , Aelita-Luiza A. Makarova , Timofey V. Ivanisenko , Ivan A. Razumov , Daria A. Kolomeyets , Sergey V. Cheresiz , Olga I. Solovieva , Kirill P. Larionov , Yulia S. Sotnikova , Yuri V. Patrushev , Nikolay A. Kolchanov , Andrey G. Pokrovsky , Nikolay A. Vinokurov , Vladimir V. Kanygin , Vasiliy M. Popik , Oleg A. Shevchenko","doi":"10.1016/j.bbalip.2025.159595","DOIUrl":"10.1016/j.bbalip.2025.159595","url":null,"abstract":"<div><div>Terahertz (THz) radiation has gained attention due to technological advancements, but its biological effects remain unclear. We investigated the impact of 2.3 THz radiation on SK-MEL-28 cells using metabolomic and gene network analysis. Forty metabolites, primarily related to purine, pyrimidine synthesis and breakdown pathways, were significantly altered post-irradiation. Lipids, such as ceramides and phosphatidylcholines, were also affected. Gene network reconstruction and analysis identified key regulators of the enzymes involved in biosynthesis and degradation of significantly altered metabolites. Mitochondrial membrane components, such as the respiratory chain complex, the proton-transporting ATP synthase complex, and components of lipid rafts reacted to THz radiation. We propose that THz radiation induces reversible disruption of the lipid raft macromolecular structure, thereby altering mitochondrial molecule transport while maintaining protein integrity, which explains the high cell survival rate. Our findings enhance the understanding of THz biological effects and emphasize the role of membrane components in the cellular response to THz radiation.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159595"},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}