Molecular and Cellular Biochemistry最新文献

{"title":"Sialotranscriptome of Simulium pertinax and functional characterization of SpVaP: a novel recombinant simuliid-specific vasodilator.","authors":"Camila Amaro Caldeira, Lucyana Keity Santana Silva, Thays Duarte de Oliveira, Andrea de Barros Pinto Viviani Cunha, Vincent Louis Viala, Bianca de Carvalho Lins Fernandes Távora, Bianca Cestari Zychar, Bruno Miranda de Almeida, Enéas de Carvalho, Emídio Beraldo Neto, Paula Andreia Lucas Calabria, Sarah Natalie Cirilo Gimenes, Eliana Faquim de Lima Mauro, Geraldo Santana Magalhaes","doi":"10.1007/s11010-026-05718-4","DOIUrl":"10.1007/s11010-026-05718-4","url":null,"abstract":"<p><p>The salivary glands of hematophagous arthropods possess a remarkable molecular diversity, reflecting evolutionary adaptations to blood feeding lifestyle and vector-host interactions. In this study, we characterized the salivary-gland transcriptome of adult female Simulium pertinax, a medically important black fly species widely distributed in South America. Through RNA sequencing and bioinformatics analyses, we identified 15,708 high-quality transcripts, of which 1947 clusters were related to secreted proteins, distributed across 23 distinct functional families, including digestive enzymes, protease inhibitors, antimicrobial peptides, and hemostasis modulators. Phylogenetic analyses of selected hematophagy-associated families, including Kunitz-domain inhibitors, Apyrases, Kazal-type inhibitors, Serpins, and SVEP homologs, revealed a combination of conserved evolutionary relationships and lineage-specific diversification among simuliids. Notably, the SVEP (Simulium Vasodilator Erythema Protein) family was highly represented and appears to be restricted to black flies. Given that its biological role remains largely uncharacterized, we selected a novel SVEP variant for heterologous expression and functional characterization, which was designated as recombinant Simulium pertinax Vasoactive Protein (rSpVaP). This recombinant protein elicited vasodilator activity in the arterioles of the mouse cremaster muscle, as well as significant paw edema. These findings support rSpVaP as a biologically active SVEP-related salivary vasoactive protein in simuliids, underscoring its contribution to facilitating blood-feeding. Taken together, these results highlight the value of combining transcriptomic profiling with functional characterization to uncover the molecular adaptations underlying hematophagy in black flies, enhancing our understanding of vector-host interactions and the evolutionary pressures shaping the sialotranscriptome.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5231-5249"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886919","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":"METTL3‑mediated OTUB1 sustains PD‑L1 protein stability via deubiquitination and promotes immune evasion in oral squamous cell carcinoma.","authors":"Dongbin Chen, Qinghua Liu, Qisong Wang, Juncai Lin, Jie Wang","doi":"10.1007/s11010-026-05732-6","DOIUrl":"10.1007/s11010-026-05732-6","url":null,"abstract":"<p><p>Immune evasion facilitates the progression of oral squamous cell carcinoma (OSCC). This study investigates how METTL3-mediated OTUB1 modulates PD-L1 ubiquitination and promotes immune evasion in OSCC. OTUB1 expression was analyzed in tumor and adjacent normal tissues from OSCC patients. OTUB1 knockdown experiments were performed in HN-6 cells. The relationship between OTUB1 and PD-L1 was detected. OTUB1-knockdown HN-6 cells were co-cultured with activated PBMCs, and tumor immunity was subsequently assessed. Tumor growth and immunity were observed in a mouse model injected with HN-6 cells transfected with si-OTUB1 and oe-PD-L1. The mechanistic interaction among METTL3, YTHDF1, and OTUB1 was determined, as well as their action in mouse tumor models. OTUB1 was upregulated in OSCC and correlated with poor prognosis. Knocking down OTUB1 directly increased PD-L1 ubiquitination levels, downregulated PD-L1 protein abundance, and weakened the binding between tumor cells and PD-1. OSCC cells with OTUB1 knockdown were co-incubated with PBMCs, resulting in enhanced apoptosis of OSCC cells, increased CD4⁺/CD8⁺ T cell infiltration, reduced FoxP3⁺ Tregs, exhausted CD8⁺ T cell subsets, and elevated GzmB/IFN-γ production. METTL3 mediated m⁶A modification of OTUB1 mRNA, which enhanced the stability of OTUB1 mRNA and upregulated OTUB1 expression through the reader protein YTHDF1. In vivo experiments confirmed that METTL3 promoted OSCC progression and immune evasion via m⁶A-dependent OTUB1 regulation and subsequent PD-L1-mediated CD8⁺ T cell suppression. METTL3 stabilizes OTUB1 mRNA through m⁶A methylation, upregulates PD-L1 expression, and promotes immune evasion, thereby accelerating OSCC progression.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5605-5620"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031047","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":"The adaptor protein ARAP contributes to Akt-dependent NF-κB p50 activation and inflammatory cytokine production in dendritic cells.","authors":"Chohee Park, Jong Ran Lee","doi":"10.1007/s11010-026-05751-3","DOIUrl":"10.1007/s11010-026-05751-3","url":null,"abstract":"<p><p>Adaptor proteins play critical roles in determining the specificity of innate immune signaling pathways. Here, we report that a previously uncharacterized adaptor protein, ARAP (activation-dependent, raft-recruited ADAP-like phospho-protein), is critical for lipopolysaccharide (LPS)-induced cytokine production in dendritic cells (DCs). Bone marrow-derived DCs (BMDCs) isolated from ARAP knockout (ARAP-KO) mice exhibited a significant reduction in proinflammatory cytokine production following LPS stimulation. Mechanistically, ARAP-KO-derived BMDCs displayed normal activation of mitogen-activated protein kinases and inhibitor of κBα (IκBα) degradation, along with preserved nuclear translocation of nuclear factor-κB (NF-κB) p65. However, the nuclear translocation of the NF-κB p50 subunit was markedly impaired. Concomitantly, LPS-induced Akt phosphorylation was attenuated in ARAP-KO-derived BMDCs. Pharmacological inhibition of Akt in wild-type BMDCs phenocopied the defect in p50 nuclear translocation. These findings reveal a non-canonical mechanism in which ARAP is required for p50 nuclear translocation in an Akt-dependent pathway, independent of classical IκB kinase-IκB signaling, adding mechanistic insight into innate immune signaling.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5697-5707"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075338","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":"Distinct molecular adaptations underlie convergent phenotypic responses to mannose in normal and metastatic melanocytes.","authors":"Nathália de Vasconcellos Racorti, Luis Roberto Fonseca Lima, Silvina Odete Bustos, Murilo Salardani, Uilla Barcick, Claudia Barbosa Ladeira de Campos, Bianca Alves Pauletti, Adriana Franco Paes Leme, Roger Chammas, André Zelanis","doi":"10.1007/s11010-026-05713-9","DOIUrl":"10.1007/s11010-026-05713-9","url":null,"abstract":"<p><p>Mannose has emerged as a promising metabolic modulator capable of impairing tumor growth in phosphomannose isomerase (PMI)-deficient cancers. However, the molecular adaptations underlying the response of melanoma cells to mannose remain poorly understood. Here, we compared the phenotypic, proteomic, and phosphoproteomic responses of normal melanocytes (Melan-A) and metastatic melanoma cells (B16F10) cultured in glucose- or mannose-containing media. Both cell types exhibited similar phenotypic responses to mannose, including reduced growth, altered lactate production, and increased accumulation of acidic vesicles. Despite these shared phenotypes, proteomic and phosphoproteomic analyses revealed markedly distinct molecular adaptations. Mannose induced modest proteomic changes in normal melanocytes but extensive remodeling in metastatic melanoma cells, accompanied by profound phosphoregulatory remodeling. Substrate enrichment analysis based on curated signaling interactions identified phosphosubstrate signatures associated with predominantly homeostatic regulatory programs in normal melanocytes, whereas metastatic cells exhibited phosphosubstrate signatures associated with stress-responsive, survival, cell-cycle, and ubiquitin-mediated regulatory programs. Collectively, our findings demonstrate that similar phenotypic responses to mannose arise from fundamentally distinct molecular programs, highlighting cellular context as a key determinant of the adaptive response to mannose-induced metabolic stress in melanoma.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5201-5212"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865955","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":"Dapagliflozin attenuates methotrexate-induced hepatorenal toxicity in rats: insights into oxidative stress, inflammation, autophagy and apoptosis.","authors":"Al Shaima G Abd El Salam, Nesma A Abd Elrazik","doi":"10.1007/s11010-026-05724-6","DOIUrl":"10.1007/s11010-026-05724-6","url":null,"abstract":"<p><p>Methotrexate (MTX) is a potent chemotherapeutic drug used to treat various malignancies, and serious autoimmune diseases. Unfortunately, the potential liver and kidney toxicities of MTX restrict its clinical effectiveness. The present study aims to explore the protective effects of dapagliflozin (Dapa) against MTX-induced hepatorenal toxicity in a rat model. Eighteen male Sprague-Dawley rats were randomly distributed into three groups; Normal, MTX and MTX + Dapa, rats received Dapa (10 mg/kg) orally once daily for 10 days; and a single i.p. injection of MTX (20 mg/kg) on the fifth day. The Dapa ameliorated hepatorenal histopathological changes induced by MTX and modulated liver and kidney function biomarkers. Dapa significantly upregulated the expression of PPAR-γ /Nrf-2/HO-1 which in turn downregulated the expression of NF-κB in hepatic and renal sections. Also, Dapa restored hepatic and renal tissues oxidative balance via significant elevation of GSH content and lowering MDA content. Moreover, Dapa modulated beclin1/LC3 dependent autophagy and caspase-3/Bcl-2 mediated apoptosis in hepatic and renal tissues. In conclusion, Dapa showed substantial hepatorenal protection against MTX-induced hepatorenal toxicity, highlighting a new therapeutic strategy in MTX treatment protocols.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5455-5469"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977255","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":"Eugenol regulates ferroptosis through Mfn2/SLC7A11/GPX4 pathway to alleviate glutamate excitotoxicity damage in glaucoma.","authors":"Qian Wang, Lemeng Feng, Cheng Zhang, Weiming Zhu, Min He, Fangbing Ye, Longqing Luo, Shiqi Qin, Zhiqi Xiong, Haifa Liu, Weitao Song, Yu Xiong","doi":"10.1007/s11010-026-05676-x","DOIUrl":"10.1007/s11010-026-05676-x","url":null,"abstract":"<p><p>Glaucoma is a leading cause of irreversible blindness, characterized by progressive loss of retinal ganglion cells (RGCs), with glutamate excitotoxicity being a key contributor to RGC damage. Eugenol, a natural phenolic compound, has been shown to exhibit neuroprotective properties. However, protective effect of eugenol on glaucoma has not been explored. This study aimed to evaluate neuroprotective effects of eugenol in models of glutamate excitotoxicity and to explore the underlying mechanisms. The glutamate-induced R28 cell excitotoxicity model and N-methyl-D-aspartate (NMDA)-induced mouse glaucoma model were established. Cell Counting Kit-8 (CCK-8), iron ion probes, lipid peroxidation detection and other techniques were employed to elucidate whether eugenol could alleviate glutamate-induced ferroptosis. Subsequently, in vivo validation was performed using C57BL/6J mice. Eugenol significantly attenuated glutamate-induced R28 cell death and RGC damage. Eugenol restored Mitofusin 2 (Mfn2) levels reduced by glutamate excitotoxicity, thereby reducing abnormal lipid droplet (LD) accumulation and alleviating mitochondrial dysfunction. Furthermore, it upregulated solute carrier family 7 member 11 (SLC7A11), increased cellular glutathione (GSH) levels, and activated glutathione peroxidase 4 (GPX4) in an Mfn2-dependent manner, ultimately inhibiting ferroptosis. Eugenol exerts neuroprotective effects in glaucoma excitotoxicity models by suppressing ferroptosis through Mfn2-mediated regulation of mitochondrial-LD homeostasis and the SLC7A11/GSH/GPX4 antioxidant pathway.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4465-4481"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630922","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":"Ckmm-Cre transgenic mice maintain phenotypic and cardiac mitochondrial homeostasis during ketogenic feeding.","authors":"Sukru Anil Dogan","doi":"10.1007/s11010-026-05672-1","DOIUrl":"10.1007/s11010-026-05672-1","url":null,"abstract":"<p><p>Conditional gene targeting using the Cre-loxP system requires validation of each Cre driver line under the specific experimental conditions to be employed, as Cre recombinase expression can cause transgene-associated pathology. The Ckmm-Cre transgenic mouse is widely used for heart- and skeletal muscle-directed conditional gene targeting, yet its phenotypic and cardiac mitochondrial response to ketogenic diet (KD) remains uncharacterized. Here we report that four-week KD feeding did not alter body weight, treadmill endurance, grip strength, locomotor activity, or rotarod performance in young male Ckmm-Cre mice. Cardiac mitochondrial oxygen consumption and hydrogen peroxide production, assessed by high-resolution respirometry, were likewise unchanged. In cardiac tissue lysates, oxidative phosphorylation subunit abundance and VDAC1 levels were maintained, with no major diet-associated changes in mitochondrial protein content. These pilot data establish a baseline reference for future conditional knockout studies employing this Cre driver under ketogenic conditions.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4355-4362"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620842","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":"NEK2 is essential for spindle assembly checkpoint regulation and cytoskeleton organization in porcine oocyte meiotic maturation.","authors":"Se-Been Jeon, Pil-Soo Jeong, Hyo-Gu Kang, Ji Hyeon Yun, Se-Yeon Eom, Na-Gyeom Oh, Yeounsun Oh, Seung Hwan Lee, Sun-Uk Kim, Seong-Keun Cho, Bo-Woong Sim","doi":"10.1007/s11010-026-05674-z","DOIUrl":"10.1007/s11010-026-05674-z","url":null,"abstract":"<p><p>NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that plays crucial roles in cellular events such as centrosome separation, cell cycle progression, spindle assembly checkpoint (SAC) regulation, and microtubule stabilization. However, its regulatory function during oocyte meiotic maturation remains unclear. In this study, NEK2 activity was inhibited using the specific inhibitor MBM-55 to evaluate its role in oocyte meiotic maturation and early embryonic development. NEK2 depletion impaired multiple indicators associated with oocyte maturation and decreased the maturation rate. Mechanistic analysis suggested that NEK2 inhibition altered spindle organization and chromosome alignment, which may be associated with impaired kinetochore-microtubule (K-MT) interactions and altered SAC-associated signaling, collectively contributing to MI-stage arrest and increased aneuploidy. In addition, NEK2 deficiency impaired the actin network, reducing spindle migration, preventing the efficient repair of accumulated DNA damage and ultimately leading to apoptosis. NEK2 inhibition in oocytes reduced subsequent embryonic developmental competence, leading to a lower blastocyst formation rate. These findings demonstrate that NEK2 is a critical regulator of porcine oocyte meiotic maturation through its roles in SAC regulation, K-MT attachment, cytoskeletal dynamics, and the DNA damage response.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4549-4564"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669950","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":"IRP1 deficiency promotes fibroblast activation through iron dysregulation: protective modulation by H₂S.","authors":"Anmol Bola, Alex McFadden, Oyine Favour Ochigbo, Hassan Mustafa Arif, Rui Wang, Kostas Pantopoulos, Guangdong Yang","doi":"10.1007/s11010-026-05698-5","DOIUrl":"10.1007/s11010-026-05698-5","url":null,"abstract":"<p><p>Iron is indispensable for core physiological processes, and intracellular iron homeostasis is tightly governed by iron regulatory protein 1 (IRP1). Hydrogen sulfide (H₂S), an endogenous gasotransmitter with well-established antioxidant and cytoprotective activities, remains poorly characterized for its regulatory roles in IRP1-dependent iron metabolism and fibroblast activation. Herein, we employed primary mouse embryonic fibroblasts (MEFs) to interrogate the functional crosstalk between NaHS (a H₂S donor) and IRP1 governing iron balance and profibrotic responses. Our results reveal that IRP1 ablation or iron supplementation elevates the labile iron pool, triggers oxidative stress, and enhances cell adhesion, proliferation, and expression of profibrotic genes. Exogenous NaHS supplementation reduced labile iron accumulation and rescued iron-evoked cellular abnormalities, with this beneficial effect predominantly observed in wild-type MEFs. Mechanistically, NaHS upregulated IRP1 aconitase activity without altering the expression of transferrin receptor 1 or ferritin heavy chain. Although IRP1 deficiency and iron overload boosted endogenous H₂S production, neither manipulation changed the protein abundance of three major H₂S-synthesizing enzymes: cystathionine gamma-lyase (CSE), cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase. In vivo, intravenous iron administration elicited markedly greater cardiac profibrotic gene expression in CSE-knockout mice relative to wild-type littermates. Taken together, these data establish that H₂S mitigates iron overload and subsequent fibrosis driven by IRP1 dysfunction, pointing toward promising therapeutic strategies for iron imbalance-associated fibrotic disorders.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4723-4737"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706983","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":"Long-chain chlorinated paraffins exposure induces premature ovarian failure by disrupting the balance of mitochondrial fission.","authors":"Chenhui Xu, Haochu Deng, Xue Tian, Shuang Ma, Yuebing Kong, Ruoting Zhang, Shiyu Yao, Hainan Lan","doi":"10.1007/s11010-026-05696-7","DOIUrl":"10.1007/s11010-026-05696-7","url":null,"abstract":"<p><p>Long-chain chlorinated paraffins (LCCPs) accumulate in reproductive organs due to their high persistence and bioaccumulation potential; however, the molecular mechanisms underlying their ovarian toxicity remain unclear. In this study, we used primary mouse granulosa cells, a human SVOG cell line, and an oral exposure model in female mice to systematically evaluate the ovarian damage effects of LCCPs and investigate the underlying signaling pathways. The results showed that concentrations of 0.02-2 µg/mL of LCCPs concentration-dependently reduced granulosa cell survival rates (by 12%-58%, P < 0.05), while significantly upregulating oxidative stress (MDA, ROS), inflammatory cytokines (IL-6, TNF-α), and aging markers (SA-β-gal activity). In vivo exposure led to morphological degeneration of ovarian tissue and a reduction in the number of primordial follicles, accompanied by decreased serum estradiol and elevated follicle-stimulating hormone (FSH) levels; these changes resemble the phenotype of clinical ovarian dysfunction. At the mechanistic level, LCCPs induce excessive mitochondrial fission by blocking the interaction between Drp1 and Parkin, leading to the leakage of mitochondrial DNA into the cytoplasm, which in turn activates the cGAS-STING pathway and ultimately drives granulosa cell senescence. These findings reveal a novel mechanism by which LCCPs mediate ovarian toxicity via the \"excessive mitochondrial fragmentation- mtDNA leakage- cGAS- STING- cellular senescence\" axis, providing direct experimental evidence for assessing the risks of persistent organic pollutants to female reproductive health.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4813-4828"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795529","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}