Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"A dynamin-like protein in Plasmodium falciparum plays an essential role in parasite growth, mitochondrial development and homeostasis during asexual blood stages","authors":"Vandana Thakur ,&nbsp;Md. Muzahidul Islam ,&nbsp;Shweta Singh ,&nbsp;Sumit Rathore ,&nbsp;Azhar Muneer ,&nbsp;Gaurav Dutta ,&nbsp;Mudassir M. Banday ,&nbsp;Priya Arora ,&nbsp;Mohammad E. Hossain ,&nbsp;Shaifali Jain ,&nbsp;Shakir Ali ,&nbsp;Asif Mohmmed","doi":"10.1016/j.bbamcr.2025.119940","DOIUrl":"10.1016/j.bbamcr.2025.119940","url":null,"abstract":"<div><div>Malaria parasites harbour a single mitochondrion, and its proper segregation during parasite multiplication is crucial for the propagation of the parasite within the host. Mitochondrial division machinery consists of several proteins that associate with the mitochondrial membrane during segregation. Here, we have identified a dynamin-like protein in <em>P. falciparum</em>, <em>Pf</em>Dyn2, and deciphered its role in mitochondrial growth and homeostasis. A GFP targeting approach combined with high-resolution microscopy studies showed that the <em>Pf</em>Dyn2 associates with the mitochondrial membrane at specific sites during mitochondrial division. The C-terminal degradation tag mediated inducible knock-down (iKD) of <em>Pf</em>Dyn2 significantly inhibited parasite growth. <em>Pf</em>Dyn2-iKD hindered mitochondrial development and functioning, decreased mtDNA replication, and induced mitochondrial oxidative stress, ultimately causing parasite death. Regulated overexpression of a phosphorylation mutant of <em>Pf</em>Dyn2 (Ser-612-Ala) did not affect the recruitment of <em>Pf</em>Dyn2 on the mitochondria; normal mitochondrial division and parasite growth showed that phosphorylation/dephosphorylation of this conserved serine residue (Ser612) may not be responsible for regulating recruitment of <em>Pf</em>Dyn2 to the mitochondrion. Overall, we show the essential role of <em>Pf</em>Dyn2 in mitochondrial development and maintaining its homeostasis during the asexual cycle of the parasite.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 5","pages":"Article 119940"},"PeriodicalIF":4.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742089","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":"Effects of CDC45 mutations on DNA replication and genome stability","authors":"Milena Denkiewicz-Kruk ,&nbsp;Deepali Chaudhry ,&nbsp;Alina Krasilia,&nbsp;Malgorzata Jedrychowska,&nbsp;Iwona J. Fijalkowska,&nbsp;Michal Dmowski","doi":"10.1016/j.bbamcr.2025.119936","DOIUrl":"10.1016/j.bbamcr.2025.119936","url":null,"abstract":"<div><div>Cdc45 is a non-catalytic subunit of the CMG helicase complex that is recruited to the autonomously replicating sequence at the onset of DNA replication. The Cdc45 protein is required for the initiation of DNA replication as well as for nascent DNA strand synthesis. It interacts with Mcm2 and Psf1 elements of CMG helicase, as well as with Sld3, an initiation factor, and Pol2, the catalytic subunit of DNA polymerase epsilon (Pol ε). In this study, we analyzed the effects of amino acid substitutions in the Cdc45 region involved in the interaction of this protein with Mcm2–7 (Cdc45-1), Psf1 (Cdc45-26), and Sld3 (Cdc45-25, Cdc45-35). We found that mutations in <em>CDC45</em> resulted in defective DNA replication. Under permissive conditions, delayed DNA synthesis was observed. At restrictive temperatures, the mutant cells were unable to efficiently replicate DNA. However, after the initiation of DNA replication under permissive conditions, the four analyzed <em>CDC45</em> mutants exhibited DNA synthesis under the restrictive conditions. Moreover, we observed increased mutation rates, mainly dependent on DNA polymerase zeta (Pol ζ), as well as increased incidence of replication errors. These findings confirm the essential function of Cdc45 in DNA replication initiation and demonstrate that impaired Cdc45 subunit has an impact on the fidelity of the nascent DNA strand synthesis. The changes in cell function observed in this study, related to defects in Cdc45 function, may help understand some diseases associated with <em>CDC45</em>.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 5","pages":"Article 119936"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727932","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":"S-phase kinase-associated protein 1 inhibits orbital fibroblasts adipogenesis to improve thyroid-associated ophthalmopathy (TAO)","authors":"Shiyao Lu,&nbsp;Wei Xiong,&nbsp;Jinping Yi,&nbsp;Shenghua Liu,&nbsp;Feng Zhang","doi":"10.1016/j.bbamcr.2025.119937","DOIUrl":"10.1016/j.bbamcr.2025.119937","url":null,"abstract":"<div><div>Thyroid-associated ophthalmopathy (TAO), a localized manifestation of Graves' disease, involves complex autoimmune interactions leading to orbital tissue inflammation and remodeling. The pathophysiology of TAO is marked by significant orbital connective tissue and fat pad expansion, mononuclear cell infiltration, and fibrosis, ultimately affecting eye motility and quality of life. This study explores the role of S-phase kinase-associated protein 1 (SKP1) in the adipogenic differentiation of orbital fibroblasts (OFs), a key process in TAO. Using bioinformatics analysis of gene expression profiles from TAO patients (GSE105149 and GSE58331), SKP1 was identified as a critical regulator of adipogenesis. Experimental validation confirmed that SKP1 expression is significantly downregulated in TAO-derived OFs under adipogenic differentiation for 10 days, correlating with elevated lipid accumulation and increased expression levels of adipogenic markers. Furthermore, downregulation of SKP1 promotes adipogenic differentiation, while upregulation inhibits this process in OFs in vitro and in TAO mice models in vivo. Mechanistically, SKP1 was shown to modulate the PI3K/AKT signaling, with downregulation activating and upregulation inhibiting the pathway, thereby influencing adipogenesis. In summary, SKP1 exerts a crucial regulatory effect on TAO pathogenesis and might act as an underlying therapeutic target for mitigating OFs adipogenesis in TAO.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 5","pages":"Article 119937"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727936","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":"Silencing of fibronectin type III domain-containing protein 3A (FNDC3A) attenuates epithelial-to-mesenchymal transition (EMT), cancer invasion, and stemness in triple-negative breast cancer (TNBC)","authors":"Nanaka Wada ,&nbsp;Satoshi Sakai ,&nbsp;Yasumichi Inoue ,&nbsp;Makoto Nishizuka","doi":"10.1016/j.bbamcr.2025.119935","DOIUrl":"10.1016/j.bbamcr.2025.119935","url":null,"abstract":"<div><div>Currently, there are no effective therapeutic targets for triple-negative breast cancer (TNBC), including hormonal therapy, and it has a poor prognosis because of its rapid proliferation, high invasiveness, and metastatic potential. Therefore, it is expected that the elucidation of the characteristics of TNBC at the molecular level may lead to the development of new therapeutic drugs. In this study, Kaplan-Meier curve analysis showed that high expression levels of fibronectin type III domain-containing protein 3A (FNDC3A) were associated with poor overall survival in patients with TNBC. Furthermore, FNDC3A knockdown was found to suppress the epithelial-to-mesenchymal transition (EMT) and invasion potential as well as the stemness in several TNBC cell lines. In addition, RNA-seq analysis revealed that FNDC3A suppression inhibited the expression of Yes-associated protein 1 (YAP1) and its target genes, which have been reported to regulate cancer cell invasion and stemness. These results suggest that FNDC3A is a novel factor that plays an important role in the malignant progression of TNBC by maintaining cancer stemness and promoting cell invasion and that its function may involve the YAP1 pathway regulation. Therefore, FNDC3A is expected to become a potential therapeutic target for patients with TNBC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 4","pages":"Article 119935"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686629","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":"Defective gating of the Sec61 translocon results in reorganisation of the actin cytoskeleton and perturbed formation of the actomyosin contractile ring","authors":"Lee V. Thomasson ,&nbsp;Christopher M. Witham ,&nbsp;Robert F.L. Steuart ,&nbsp;Danielle E. Dye ,&nbsp;Carl J. Mousley","doi":"10.1016/j.bbamcr.2025.119932","DOIUrl":"10.1016/j.bbamcr.2025.119932","url":null,"abstract":"<div><div>The Sec61 complex sits between the distinct environments of the cytosol and the ER lumen and it's appropriate gating is essential to prevent the deleterious flux of molecules and ions between them. Using the <em>sss1–7</em> mutant we show that actin dynamics is grossly perturbed when translocon gating is defective. Importantly, normal actin morphology is restored when <em>sss1–7</em> translocon gating defects are suppressed or when these cells are treated with cell-permeable Ca²⁺ chelators. Our findings underscore the importance of translocon gating, particularly in regulating Ca²⁺ homeostasis, in the overall regulation and functional distribution of the actin cytoskeleton.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 4","pages":"Article 119932"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668969","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":"Transcription factor EP300 targets SIRT5 to promote autophagy of nucleus pulposus cells and attenuate intervertebral disc degeneration","authors":"Xiao-wei Liu ,&nbsp;Shan-shan Huang ,&nbsp;Pei Xu ,&nbsp;Hao-wei Xu ,&nbsp;Dian-kai Wang ,&nbsp;Shan-jin Wang","doi":"10.1016/j.bbamcr.2025.119933","DOIUrl":"10.1016/j.bbamcr.2025.119933","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IVDD) is a prevalent spinal ailment and the leading cause of chronic low back pain. Understanding the exact pathogenesis of IVDD and developing targeted molecular drugs will be important in the future. Autophagy plays a key role in the metabolic processes and in the quality control of proteins in IVDD. However, the role of autophagy in the senescence of nucleus pulposus cell (NPC), the primary cells in the intervertebral disc responsible for maintaining the disc's structure and function, is not yet clear.</div></div><div><h3>Methods</h3><div>Gene expression profiling data of human disc tissue were obtained from the Gene Expression Omnibus <span><span>GSE15227</span><svg><path></path></svg></span>, <span><span>GSE23130</span><svg><path></path></svg></span>, and <span><span>GSE70362</span><svg><path></path></svg></span> datasets. Autophagy-related differentially expressed genes were identified from the Molecular Signatures Database (MSigDB) database. Weighted gene co-expression network analysis (WGCNA), receiver operating characteristic (ROC) curves, and least absolute shrinkage and selection operator (LASSO) regression identified an autophagy-related hub gene that encodes the E1A binding protein EP300 transcription factor in IVDD samples. Potential downstream target genes of EP300 were identified by bioinformatics analysis. The analysis identified sirtuin 5 (<em>SIRT5</em>) as a potential downstream target of EP300. Chromatin immunoprecipitation (ChIP)-qPCR, small interfering RNA (siRNA), and luciferase reporter gene assays were used to verify the interaction of EP300 and <em>SIRT5</em> in vitro. For in vivo experiments, <em>SIRT5</em> knockout mice and <em>SIRT5</em>-overexpressing adeno-associated virus serotype 5 (AAV5) were constructed to verify the effect of the EP300–<em>SIRT5</em> signal axis on the progression of IVDD.</div></div><div><h3>Results</h3><div><em>EP300</em> expression was reduced in the IVDD samples compared with its expression in healthy disc tissue samples. The reduced <em>EP300</em> expression inhibited the occurrence of autophagy, which promoted NPC senescence. ChIP-qPCR and luciferase reporter gene assays showed that EP300 promoted <em>SIRT5</em> expression by direct binding to its promoter. Activation of <em>EP300</em> expression increased <em>SIRT5</em> expression and significantly improved autophagy for inhibition of NPC senescence. In vivo experiments confirmed that knockdown of <em>EP300</em> promoted NPC senescence and led to an exacerbation of IVDD, which was reversed by <em>SIRT5</em> overexpression.</div></div><div><h3>Conclusion</h3><div>Our results provide the first evidence for the importance of EP300 and <em>SIRT5</em> interactions in promoting IVDD development by inhibiting autophagy during IVDD. The EP300–<em>SIRT5</em> signaling axis was identified as a promising target for therapy of IVDD based on autophagy genes.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 4","pages":"Article 119933"},"PeriodicalIF":4.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647031","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":"Metformin attenuates myocardial ischemia/reperfusion-induced ferroptosis through the upregulation of Nur77-mediated IDH1","authors":"Zhenhua Wu ,&nbsp;Yunpeng Bai ,&nbsp;Chao Chang ,&nbsp;Yan Jiao ,&nbsp;Qinliang Chen ,&nbsp;Zhigang Guo","doi":"10.1016/j.bbamcr.2025.119934","DOIUrl":"10.1016/j.bbamcr.2025.119934","url":null,"abstract":"<div><div>Current interventions for myocardial ischemia/reperfusion (I/R) injury focus on revascularization and the control of oxidative stress. Metformin can reduce I/R injury, with its protective effects extending beyond metabolic regulation. In this study, we investigated the cardioprotective mechanisms of metformin beyond AMPK activation, focusing on its effects on the Nur77-IDH1 axis. We employed myocardial I/R rat models and oxygen-glucose deprivation/reoxygenation in H9C2 cells, utilizing staining techniques, echocardiography, and molecular/cell-based assays. Metformin significantly mitigated myocardial I/R injury in rats, reducing <em>PTGS2</em> expression, lowering iron content, decreased ROS accumulation, and increased mitochondrial function. Metformin also alleviated myocardial tissue damage and fibrosis and increased survival rates. In OGD/R-induced H9C2 cells, metformin suppressed ferroptosis, which could be reversed by Nur77 silencing. Metformin increased Nur77 and IDH1 expression by enhancing Nur77 translocation to the IDH1 promoter, inhibiting stress-related JNK/P38MAPK signaling. Catalytic site inhibitor IDH1 Inhibitor 5 (compound 2 AGI-5198) negated the protective effects of metformin. Collectively, these data reveal that metformin prevents myocardial I/R injury and ferroptosis through its effects on Nur77, IDH1 expression and inhibition of the JNK/P38 pathway. This highlights the novel therapeutic value of targeting ferroptosis with metformin to improve cardiac protection.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 4","pages":"Article 119934"},"PeriodicalIF":4.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646938","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":"Increasing collagen synthesis in fibroblasts: The roles of PCL microspheres and the SAMD11–PLOD1 axis in skin rejuvenation","authors":"Mibu Cao ,&nbsp;Li Tao ,&nbsp;Youliang Zhang ,&nbsp;Lingcong Zhou ,&nbsp;Shu Wu ,&nbsp;Haoxian Zhou ,&nbsp;Yuanlong Ge ,&nbsp;Ying Zou ,&nbsp;Shengkang Luo","doi":"10.1016/j.bbamcr.2025.119931","DOIUrl":"10.1016/j.bbamcr.2025.119931","url":null,"abstract":"<div><div>The degradation of extracellular matrix proteins such as collagen and elastin with aging leads to skin sagging. Polycaprolactone (PCL) microspheres are used as facial fillers because of their ability to provide volume, biodegradability, and collagen-stimulating properties. The direct biological effects of PCL microspheres on fibroblasts, particularly in stimulating sustained collagen production, require further investigation. We detected the safety and effect of PCL microspheres on human fibroblasts and investigated new collagen synthesis and the thickness of C57BL/6 mouse skin. Through an RNA-seq analysis of differentially expressed genes, we identified a key regulator of collagen production in PCL-stimulated fibroblasts. Our research revealed that PCL microspheres are safe for human fibroblasts, promoting their proliferation and increasing new collagen synthesis and skin thickness. We identified sterile alpha motif domain containing 11 (SAMD11) as a key regulator of collagen production in PCLstimulated fibroblasts through an RNA-seq analysis. By increasing SAMD11 expression, PCL microspheres increase collagen synthesis and rejuvenate skin through the upregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1). This study elucidates the mechanism by which SAMD11 regulates the effects of PCL microspheres as collagen stimulants for skin rejuvenation, providing a foundation for the future development and refinement of similar materials.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 4","pages":"Article 119931"},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613181","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":"Effect of claudin-1 or -3 expression on cation and water channel properties of claudin-2","authors":"Fabián Martínez-Perafán ,&nbsp;Anja Fromm ,&nbsp;Rozemarijn E. van der Veen ,&nbsp;Ayk Waldow ,&nbsp;Martin Lehmann ,&nbsp;Susanne M. Krug ,&nbsp;Dorothee Günzel ,&nbsp;Rita Rosenthal ,&nbsp;Michael Fromm ,&nbsp;Jörg Piontek","doi":"10.1016/j.bbamcr.2025.119930","DOIUrl":"10.1016/j.bbamcr.2025.119930","url":null,"abstract":"<div><div>Claudin-2 (Cldn2) is a typical tight junction protein of leaky epithelia that forms paracellular channels for small cations and water. Claudin-3 (Cldn3) and claudin-1 (Cldn1) are barrier formers and may interact with Cldn2. We aimed to investigate whether this interaction affects the permeability of Cldn2 channels to ions and/or water. To achieve this, two knockout kidney cell lines (MDCK C7/Cldn3KO and MDCK II/quinKO) were used to express Cldn2 and Cldn2/Cldn3. Furthermore, MDCK II/quinKO/Cldn2/Cldn1 cells were generated for comparison. Electrophysiological assays were performed to evaluate the function and properties of Cldn2 channels in these cell models. <em>Cis-</em> and <em>trans</em>-interaction of Cldn2 with Cldn1 or Cldn3 was assessed in MDCK II/quinKO cells by FRET and enrichment assays, respectively. At the tight junction, Cldn2 had a closer <em>cis</em>-proximity to Cldn1 than to Cldn3, but a stronger <em>trans</em>-interaction with the latter. In comparison to cells expressing Cldn2 alone, co-expression with Cldn3 (in both cell models) or Cldn1 (in MDCK II/quinKO cells) resulted in lower cation permeabilities without altering the Eisenman sequences. Other than ion permeability, water flux showed no differences between MDCK C7/Cldn3KO cells expressing Cldn2 and those co-expressing Cldn2/Cldn3. Based on these results, we propose a model in which Cldn2-Cldn1 <em>cis</em>- and Cldn2-Cldn3 <em>trans</em>-interaction leads to a mixture of homo-oligomeric Cldn2 and hetero-oligomeric Cldn2/Cldn1 or Cldn2/Cldn3 channels. The latter would have a pore center where charges are neutralized, by this impairing cation permeability while still allowing water to pass.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 4","pages":"Article 119930"},"PeriodicalIF":4.6,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603876","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":"Arylamine N-acetyltransferase 1 expression predicts glucose dependence and mitochondrial bioenergetics in cancer cells","authors":"Chandra Choudhury,&nbsp;Neville J. Butcher,&nbsp;Rodney F. Minchin","doi":"10.1016/j.bbamcr.2025.119929","DOIUrl":"10.1016/j.bbamcr.2025.119929","url":null,"abstract":"<div><div>To investigate the effects of varying NAT1 activity in different cell lines, mitochondrial oxidative phosphorylation, aerobic glycolysis and mitochondrial fuel usage was quantified in a panel of human cell lines. As NAT1 activity increased, mitochondrial reserve respiratory capacity increased while aerobic glycolysis decreased. In addition, phosphorylation of PDH-E1α in these cells limited their ability to use glucose as a primary fuel source. Those cells with high NAT1 activity exhibited a quiescent metabolic phenotype and proliferated more slowly. This might explain, in part, why some cancer patients with low NAT1 expression in their tumour tissue show poorer survival outcomes compared to those with high NAT1 expression. The current study demonstrated that NAT1 enzymatic activity is important for metabolism in cancer cell lines and increasing NAT1 activity may better equip cells to survive under stressed conditions by increasing reserve respiratory capacity.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 4","pages":"Article 119929"},"PeriodicalIF":4.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584446","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}