Biochimica et biophysica acta. General subjects最新文献

{"title":"Phase separation via protein-protein and protein-RNA networks coordinates ribosome assembly in the nucleolus","authors":"Priyanka Dogra ,&nbsp;Richard W. Kriwacki","doi":"10.1016/j.bbagen.2025.130835","DOIUrl":"10.1016/j.bbagen.2025.130835","url":null,"abstract":"<div><div>The nucleolus, the largest membraneless organelle in the nucleus, functions as the site for ribosome biogenesis. While long known for its complex and dynamic structure, our mechanistic understanding of nucleolar organization has advanced dramatically in the past 15 years. The process of phase separation (PS) facilitates the compartmentalization of ribosomal components with assembly factors in the nucleolus, underlying complex ribosome biogenesis processes. Multicomponent PS creates multiple nucleolar sub-compartments that function from inside out as a ribosome assembly line. In this review, we discuss the molecular basis of nucleolar organization, including how different types of protein-protein and protein-RNA interactions create the multilayered architecture that enables ribosome biogenesis. Key proteins including nucleolin, fibrillarin, and nucleophosmin mediate nucleolar compartmentalization through their unique structural features and multivalent interactions. The processes of ribosomal RNA (rRNA) transcription, modification and splicing, and folding are spatially and temporally segregated within different regions of the nucleolus. rRNA matures and changes form along this processing continuum, continually altering its interactions with proteins, creating multiple separate liquid phases that establish sub-compartments. We highlight how both folded domains and intrinsically disordered regions (IDRs) in nucleolar proteins contribute to multivalent interactions underlying PS and nucleolar compartmentalization. We also discuss how perturbation of nucleolar PS alters nucleolar structure, dynamics, and function and contributes to a range of pathological conditions.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130835"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633262","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":"MiR-2779-x, a key microRNA that is related to the tumorigenicity of the MDCK cell line","authors":"Di Yang ,&nbsp;Lingwei Huang ,&nbsp;Jiachen Shi ,&nbsp;Zhenbin Liu ,&nbsp;Jiamin Wang ,&nbsp;Zhongren Ma ,&nbsp;Ayimuguli Abudureyimu ,&nbsp;Zilin Qiao ,&nbsp;Jianguo Chen","doi":"10.1016/j.bbagen.2025.130843","DOIUrl":"10.1016/j.bbagen.2025.130843","url":null,"abstract":"<div><div>The tumorigenicity of MDCK cell line is a major concern with respect to its safety for vaccine production, the effect of miRNAs on the tumorigenicity of MDCK cells is poorly understood. In this study, we performed miRNA-Seq on two MDCK cell lines with tumorigenic potential and their derived monoclonal cell lines that lack tumorigenicity. Through bioinformatics analysis, we identified differentially expressed miRNAs and conducted GO and KEGG pathway analyses of their target genes. Our results indicated that miR-2779-x and its target genes exhibited the most significant characteristics associated with tumorigenesis. Injection of live cells overexpressing miR-2779-x into nude mice resulted in a markedly reduced tumorigenesis rate (1/10). Overexpression of miR-2779-x significantly decreased the proliferation and migration capabilities of MDCK cells while enhancing their invasive potential. To identify and localize miR-2779-x target genes, we employed bioinformatics prediction, RT-qPCR, immunofluorescence assays (IFA), fluorescence in situ hybridization (FISH), and dual-luciferase reporter assays. We found that miR-2779-x negatively regulates the expression of PI3KR1 and Caspase 9 at both the gene and protein levels. Additionally, miR-2779-x co-localizes with PI3KR1 in the cytoplasm and directly targets the 3’UTR of PI3KR1. Overexpression of PI3KR1 in miR-2779-x-overexpressing cells restored cellular functions, leading to increased proliferation and migration but decreased invasion. Moreover, miR-2779-x modulates MDCK cell growth and tumorigenesis by influencing the expression and phosphorylation levels of proteins involved in the PI3K/AKT and apoptosis signaling pathways. We proposed the key pathways of miRNA involvement in MDCK cell tumorigenicity and initially revealed the function of miR-2779-x in MDCK cell tumorigenicity.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130843"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673880","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":"Coupling of muscarinic receptors to protein kinase C underlies a feedback regulation of cell responsiveness to acetylcholine","authors":"Ekaterina A. Dymova,&nbsp;Olga A. Rogachevskaja,&nbsp;Vladislav V. Sokolov,&nbsp;Elizaveta Е. Kopylova,&nbsp;Natalia V. Kabanova,&nbsp;Stanislav S. Kolesnikov","doi":"10.1016/j.bbagen.2025.130844","DOIUrl":"10.1016/j.bbagen.2025.130844","url":null,"abstract":"<div><div>Acetylcholine (ACh)-induced Ca²⁺ signaling was analyzed in HEK-293 (WT-HEK) cells and their derivatives, IP3R1-HEK, IP3R2-HEK, and IP3R3-HEK with a single functional IP₃ receptor isoform, IP₃R1, IP₃R2, or IP₃R3, respectively. The initial stimulation of WT-HEK cells triggered a prolonged feedback process that diminished their responsiveness to ACh. Inhibition of protein kinase C (PKC) with Gö 6983 or calphostin C prevented the decline of ACh responsivity, indicating that PKC was involved. Using IP3R1-HEK, IP3R2-HEK, and IP3R3-HEK cells, it was shown that PKC was capable of regulating Ca²⁺ release through each IP₃R isoform. While in control, IP₃ uncaging triggered Ca²⁺ transients in ∼15 % of cells loaded with caged-Ins(145)P3/PM, PKC inhibition enlarged this fraction nearly twofold. These observations suggested that in ACh transduction machinery, PKC targeted primarily IP₃-driven Ca²⁺ release. ADP and 5-HT triggered Ca²⁺ transients in WT-HEK cells and CHO cells expressing endogenous P2Y and recombinant 5HT2C receptors, respectively. The responsiveness of WT-HEK cells to ADP and CHO cells to 5-HT applied serially declined after the initial cell stimulation but PKC inhibition precluded this phenomenon almost completely. The coupling of GPCRs to PKC in living cells, muscarinic and P2Y receptors in WT-HEK cells and 5HT2C receptors in CHO cells, was demonstrated for the first time using real-time fluorescence imaging and sapphireCKAR, a genetically encoded sensor of PKC activity. Altogether, our findings suggest that a PKC-based feedback regulation of agonist-induced Ca²⁺ release might be a common attribute of transduction of various agonists involving GPCRs coupled to the phosphoinositide cascade.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130844"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717301","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":"IRF1 transcriptionally activates ALOX15B to enhance ferroptosis sensitivity in triple-negative breast cancer","authors":"Wei Peng,&nbsp;Yi Xie,&nbsp;Bofeng Duan,&nbsp;Fuyong Qian,&nbsp;Zhifeng Fan,&nbsp;Wei Zheng","doi":"10.1016/j.bbagen.2025.130846","DOIUrl":"10.1016/j.bbagen.2025.130846","url":null,"abstract":"<div><div>This study focused on the transcriptional activation of arachidonate 15-lipoxygenase type B (ALOX15B) by interferon regulatory factor 1 (IRF1) to promote ferroptosis in triple-negative breast cancer (TNBC) cells. In this study, TNBC and adjacent non-cancerous tissues were collected to detect ALOX15B expression. Functional studies were conducted by overexpressing or knocking down ALOX15B in TNBC cells treated with erastin (a ferroptosis inducer). The role of IRF1 as a potential transcriptional regulator of ALOX15B was explored using bioinformatics tools, dual-luciferase reporter gene assays, electrophoretic mobility shift assays (EMSA), and chromatin immunoprecipitation (ChIP) followed by quantitative polymerase chain reaction (qPCR). Our results revealed that ALOX15B expression was significantly lower in TNBC tissues compared to adjacent non-cancerous tissues. Functionally, ALOX15B overexpression inhibited ferroptosis-related proteins SLC7A11 and GPX4, decreased cell viability and glutathione levels, and increased malondialdehyde levels, reactive oxygen species levels, and lipid oxidation. Conversely, knocking down ALOX15B had the opposite effect. Bioinformatics analysis predicted IRF1 as a potential transcriptional regulator of ALOX15B, which was confirmed using dual-luciferase reporter gene assays, EMSA, and ChIP-qPCR. IRF1 overexpression increased ALOX15B expression and promoted ferroptosis in TNBC cells, while IRF1 knockdown had the opposite effect. Importantly, knocking down IRF1 and overexpressing ALOX15B simultaneously demonstrated that IRF1 enhanced TNBC cell ferroptosis sensitivity by promoting ALOX15B expression. Collectively, our study suggests that IRF1 transcriptionally activates ALOX15B to enhance ferroptosis sensitivity in TNBC cells. These findings provide new insights into the molecular mechanisms underlying TNBC progression and suggest potential therapeutic targets for TNBC treatment.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130846"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757771","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":"Nitrosative stress affects mitochondrial respiratory chain complex II and complex IV assemblies in Saccharomyces cerevisiae: S-nitrosylation of complex II","authors":"Sanchita Biswas ,&nbsp;Ayantika Sengupta ,&nbsp;Shubhojit Das ,&nbsp;Chirandeep Dey ,&nbsp;Rajib Sengupta ,&nbsp;Alok Ghosh ,&nbsp;Sanjay Ghosh","doi":"10.1016/j.bbagen.2025.130845","DOIUrl":"10.1016/j.bbagen.2025.130845","url":null,"abstract":"<div><div>The elevated level of nitric oxide (NO) and reactive nitrogen species (RNS) induce nitrosative stress in cells and inhibit mitochondrial respiration. Reports showed that RNS rapidly inactivate complex I, followed by inhibition of complex II, III and IV in isolated mitochondria. However, the mechanism(s) by which NO and RNS inhibit these complexes still unclear. In this study facultative anaerobic yeast <em>Saccharomyces cerevisiae</em> has been used for investigating mitochondrial respiratory dysfunction under nitrosative stress, as four out of five mitochondrial oxidative phosphorylation complexes i.e. complexes II, III, IV and V are structurally conserved from yeast to human. Using microbiological growth assays, we showed that <em>S. cerevisiae</em> wild type W3O3 cells treated with graded concentration of sodium nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) induce nitrosative stress, and cell growth was severely compromised under the respiratory proficient rich glycerol-ethanol media. Both the whole cell and the mitochondrial oxygen consumption rates were also significantly compromised under nitrosative stress. Surprisingly, mitochondrial respiratory chain complex II succinate dehydrogenase (SDH) of <em>S. cerevisiae</em> was found S-nitrosylated and therefore inactivated under nitrosative stress. Endogenous RNS produced by S-nitrosoglutathione reductase mutant cells of <em>S. cerevisiae</em> also showed increased S-nitrosylation of SDH. Complex III and IV activities were irreversibly inhibited in <em>S. cerevisiae</em> under nitrosative stress. Interestingly, protein tyrosine nitration was also enhanced in mitochondria in a dose dependent manner upon SNP treatment. Reduced expressions of both Sdh2 (succinate dehydrogenase subunit-2) and Cox2 (mitochondrial complex IV subunit) were observed at the transcription and translation level in <em>S. cerevisiae</em> under nitrosative stress. Blue Native-PAGE followed by Western blotting analysis, further revealed significantly reduced native complex II and the complex III and IV containing super-complexes assemblies in consequences of nitrosative stress in <em>S. cerevisiae</em>. Henceforth, the present in vivo study provides for the first-time novel information on the modification of mitochondrial complexes under nitrosative stress which in turn regulates the mitochondrial respiratory chain complexes assembly in <em>S. cerevisiae</em>.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130845"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764457","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":"Pharmacological role of MLN4924 in cisplatin-induced acute kidney injury","authors":"Feng Chen ,&nbsp;Ayinigaer Yusufu ,&nbsp;Gang Li ,&nbsp;Xueyun Gao ,&nbsp;Danqin Lu ,&nbsp;Xiaoyan Wu ,&nbsp;Lihua Ni","doi":"10.1016/j.bbagen.2025.130842","DOIUrl":"10.1016/j.bbagen.2025.130842","url":null,"abstract":"<div><h3>Background</h3><div>Cisplatin-induced acute kidney injury (Cis-AKI) is a major complication that limits the clinical use of cisplatin, largely due to its cytotoxic effects on renal tubular epithelial cells. Recent studies have shown that MLN4924, a NEDD8-activating enzyme inhibitor, can modulate key cellular processes such as apoptosis, autophagy, and DNA damage repair. However, its precise role and regulatory mechanisms in the context of Cis-AKI remain largely undefined.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the renoprotective mechanisms of MLN4924 in Cis-AKI.</div></div><div><h3>Materials and methods</h3><div>A cisplatin-induced nephrotoxicity mouse model and a human renal tubular epithelial (HK−2) damage cellular model were established. Kidney injury was evaluated by histopathology and RNA-sequencing. To explore whether MLN4924 alleviates Cis-AKI via modulation of the p53 and MAPK pathways, we analyzed pathway-specific regulatory changes in response to MLN4924 treatment.</div></div><div><h3>Results</h3><div>Compared to the group exposed to cisplatin, MLN4924 mitigated the pathological alterations and reduced the expression of molecules associated with renal injury. RNA-sequencing analysis indicated that the p53 and MAPK signaling pathways were inhibited by MLN4924 treatment compared to the cisplatin-exposed group. Moreover, silencing p53 or p38 exacerbates the renal protection conferred by MLN4924 in cisplatin-treated HK-2 cells, while their activation abolishes this effect. Mechanically, p38 activity promoted p53-dependent nephrotoxicity by increasing p53 expression.</div></div><div><h3>Conclusions</h3><div>MLN4924 exhibits a protective effect against Cis-AKI, as evidenced by inhibition of p53 and MAPK signaling pathways. These results suggest that MLN4924 holds potential as an adjuvant therapeutic agent in the treatment of kidney diseases associated with chemotherapy.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130842"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633598","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":"Editorial: Nondomain biopolymers – Flexible molecular strategies for diverse biological processes","authors":"Shinichi Nakagawa","doi":"10.1016/j.bbagen.2025.130847","DOIUrl":"10.1016/j.bbagen.2025.130847","url":null,"abstract":"","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130847"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803357","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":"Gamma radiation assisted green synthesis of spirulina-reduced graphene oxide and its anti-inflammatory effect against renal injury induced by gamma irradiation via IRE1α -TRAF2 pathway","authors":"M.M. Atta ,&nbsp;Marwa A. Mohamed ,&nbsp;Aliaa Mazhar ,&nbsp;Fatma Y. Abdou ,&nbsp;E.O. Taha ,&nbsp;Mahmoud E. Habieb","doi":"10.1016/j.bbagen.2025.130840","DOIUrl":"10.1016/j.bbagen.2025.130840","url":null,"abstract":"<div><h3>Background</h3><div>Combining gamma rays with natural antioxidants leads to the formation of reduced graphene oxide (RGO) biocomposites from graphene oxide (GO) in a way that is both incredibly safe and environmentally friendly, unlocking new possibilities for medical use.</div></div><div><h3>Methods</h3><div>In the present study, spirulina-reduced graphene oxide nanocomposites (SRGOs) were fabricated by gamma rays as a one-step and straightforward technique.The loading and reduction of graphene oxide in the presence of different spirulina ratios (25, 50, 100, and 200 wt%) under gamma irradiation were verified by diverse characterization apparatuses, including XRD, FTIR, HRTEM, and XPS. Moreover, in vivo studies are conducted to investigate the anti-inflammatory properties of the selected SRGO nanocomposite in preventing kidney injury caused by gamma irradiation.</div></div><div><h3>Results</h3><div>SRGO amended the renal levels of interleukin-6 (IL-6), IL-8, Inositol requirement enzyme 1α (IRE1α), and TNF receptor-associated factor 2 (TRAF2), the protein expression of NF-κB p65, and the levels of GSH, MDA, serum urea, and creatinine. In the context of oxidative stress and inflammatory biomarkers, the histopathological study results of kidney tissue concurred with those of the molecular biochemical examinations.</div></div><div><h3>Conclusion</h3><div>The findings endorsed SRGO biocomposite as a promising antioxidant, radioprotector, and anti-inflammatory agent in mitigating kidney damage caused by γ-radiation via significant inhibition of the IRE1α-TRAF2 signaling pathway.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 10","pages":"Article 130840"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633597","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 ,&nbsp;Xia Gao ,&nbsp;Ning Wang ,&nbsp;Yuping Xie ,&nbsp;Yuedi Tang","doi":"10.1016/j.bbagen.2025.130834","DOIUrl":"10.1016/j.bbagen.2025.130834","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>Utilizing The Cancer Genome Atlas (TCGA) database (<em>n</em> = 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 9","pages":"Article 130834"},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","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":"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":"2025-08-01","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}