Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"Synthesis, characterization and size-dependent cytotoxicity of magnesium ammonium phosphate hexahydrate crystals of different sizes on renal epithelial cells","authors":"Run-Min Tan ,&nbsp;Xin-Yi Tong ,&nbsp;Wen-Xuan Dai,&nbsp;Jia-Yi Zhang,&nbsp;Jian-Ming Ouyang","doi":"10.1016/j.bbamcr.2025.120022","DOIUrl":"10.1016/j.bbamcr.2025.120022","url":null,"abstract":"<div><div>Magnesium ammonium phosphate hexahydrate (MAP) crystals with sizes of 98.5 ± 20.6 nm, 310 ± 67 nm, 1.12 ± 0.34 μm, and 3.23 ± 0.90 μm were synthesized and characterized. These crystals can cause damage to renal tubular epithelial cells (HK−2), which is manifested by crystal-induced cell morphological changes, cell viability, a decrease in superoxide dismutase and mitochondrial membrane potential. In addition, there were crystal-induced increases in reactive oxygen species, lactate dehydrogenase, and malondialdehyde levels, as well as phosphatidylserine ectropion. That is, MAP crystals can lead to cell necrosis and apoptosis, and promote the release of inflammatory cytokines IL-18 and IL-6. The cytotoxicity of MAP crystals has a size effect, that is, the cytotoxicity is: MAP-100 nm &gt; MAP-300 nm &gt; MAP-1 μm &gt; MAP-3 μm. The factors enhancing the cytotoxicity of MAP include small size, large specific surface area, and a more negative crystal surface zeta potential. Nano-crystal MAP-100 nm mainly causes cell death by inducing extensive cell necrosis. When the larger-sized MAP-300 nm, MAP-1 μm and MAP-3 μm crystals acted on HK-2 cells, cell necrosis, apoptosis and autophagy occurred simultaneously. Investigating the relationship between MAP crystal size and cytotoxicity may provide insights into elucidating the mechanism of MAP stone (struvite) formation and preventing its occurrence.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120022"},"PeriodicalIF":4.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636064","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":"Deubiquitinases in metabolic diseases, fibrosis and cancer of the liver","authors":"Ananya Thakur,&nbsp;Kateryna Kubaichuk,&nbsp;Thomas Kietzmann","doi":"10.1016/j.bbamcr.2025.120021","DOIUrl":"10.1016/j.bbamcr.2025.120021","url":null,"abstract":"<div><div>Obesity is a key driver of the progression from metabolic dysfunction-associated steatotic liver disease (MASLD), to metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and hepatocellular carcinoma (HCC). Excess adiposity and elevated circulating fatty acids disrupt metabolic, inflammatory, and signaling pathways, creating conditions permissive for hepatic injury, inflammation, fibrogenesis, and carcinogenesis. One of the mechanisms that regulates these pathways is ubiquitylation, a post-translational modification that controls protein degradation and cellular signaling. Deubiquitinases (DUBs) counterbalance this process by removing ubiquitin chains, thereby maintaining cellular homeostasis.</div><div>This review examines the role of DUBs in obesity-induced MASLD progression, focusing on how dysregulated DUB expression affects insulin signaling, lipogenesis, inflammation, and oxidative stress. While DUBs have been extensively studied in cancer and metabolic syndrome, their therapeutic potential in obesity-related MASH, liver fibrosis, and HCC has not been fully explored.</div><div>By synthesizing clinical and experimental evidence, we highlight DUBs as promising precision medicine tools for both patient stratification and therapeutic intervention. This review emphasizes the critical need for further translational research to develop DUB-targeted strategies for early intervention in MASLD progression.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120021"},"PeriodicalIF":4.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623698","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":"Modulation of mitochondrial quality control through autophagic pathway in familial Alzheimer's disease","authors":"Adriana Limone ,&nbsp;Clelia Di Napoli ,&nbsp;Giusy De Rosa ,&nbsp;Silvia Bagnoli ,&nbsp;Antonella Izzo ,&nbsp;Claudio Procaccini ,&nbsp;Giuseppe Matarese ,&nbsp;Benedetta Nacmias ,&nbsp;Antonio Lavecchia ,&nbsp;Daniela Sarnataro","doi":"10.1016/j.bbamcr.2025.120019","DOIUrl":"10.1016/j.bbamcr.2025.120019","url":null,"abstract":"<div><div>Autophagy is a highly conserved cellular catabolic process recognized as an essential pathway for the maintenance of cellular homeostasis. Growing evidence implicates autophagic dysfunction in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease (AD), thus its modulation might represent an interesting therapeutic tool. Searching for a compound that stimulates autophagic pathway, led us to identify the inhibitor of RPSA receptor, NSC47924. In this study, we show that, NSC47924 down-modulated Akt-mTOR-axis pathway, the master regulator of autophagy, which was abnormally hyperactivated in fibroblasts from genetic AD-affected patients. Consistently, by monitoring the conversion of LC3, we found that inhibition of RPSA enhanced and restored the compromised autophagic flux. Moreover, by qRT-PCR analysis we found that inhibitor treatment upregulated the expression of autophagy-linked genes.</div><div>Importantly, AD-affected fibroblasts exhibited massive mitochondrial network fragmentation and mitophagy defects, which were restored through the stimulation of autophagy induced by RPSA inhibition. Consistent with an efficient elimination of dysfunctional mitochondria, we found that the turnover of both the mitophagy regulators PINK1 and Parkin and the autophagic receptors p62, NDP52, OPTN, was modulated, thus restoring a highly interconnected organelle's network. In addition, the improvement of mitochondrial morphology correlated with a functional recovery, as assessed by Seahorse analysis and mitochondrial ROS production evaluation. Collectively, our findings suggest that RPSA inhibition stimulates an autophagic pathway promoting the efficient removal of damaged mitochondria, favouring the recovery of cellular homeostasis, and counteracting crucial AD pathogenic mechanisms.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120019"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599237","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":"Epigenetic targeting of DNA damage response (DDR)-related mechanisms to overcome acquired cisplatin resistance of tumor cells","authors":"Marlena Sekeres ,&nbsp;Daniel Lengle ,&nbsp;Lena Abbey ,&nbsp;Matthias Ulrich Kassack ,&nbsp;Fabian Fischer ,&nbsp;Thomas Kurz ,&nbsp;Gerhard Fritz","doi":"10.1016/j.bbamcr.2025.120018","DOIUrl":"10.1016/j.bbamcr.2025.120018","url":null,"abstract":"<div><div>Mechanisms of the DNA damage response (DDR) are considered as useful targets to overcome tumor cell resistance. We investigated the impact of various classes of histone deacetylase inhibitors (HDACi) (i.e. broad-spectrum HDACi (vorinostat), class I HDACi (entinostat), preferential class IIb HDAC6i (ricolinostat) and dual HDAC class I/IIb inhibitors (HDAC1/6i)) on mechanisms of the DDR using parental (J82^WT) and cisplatin (CisPt)-resistant bladder carcinoma cells (J82^CisR). Mono-treatment with entinostat revealed relatively low genotoxic and DDR-activating potency, while showing similar antiproliferative, cytotoxic and pro-apoptotic activities as the other HDACi. Despite its low DNA double-strand break (DSB) forming potency with mono-treatment, entinostat conferred the highest synergistic cytotoxicity (CI ≤ 0.8) in J82^CisR following co-treatment with cisplatin. Notably, this effect is independent of Pt-(GpG)-DNA-intrastrand-crosslink formation. Entinostat increased the level of CisPt-induced DNA strand-breaks, promotes replication and transcription blockage, pRPA32 foci formation, PARP- and caspase-7 cleavage, influenced the activation of DDR-related factors (e.g. γH2AX, pp53, pRPA32, pKap1), reverted CisPt-induced p53 acetylation and blocked drug-stimulated mRNA expression of multiple DSB (HR, NHEJ)- and BER repair-related factors. Summarizing, the class I-selective HDACi entinostat reveals the lowest DDR-activating potency in mono-treatment and the highest anticancer efficacy in combination with CisPt, likely involving inhibition of HDAC3. This is due to amplification of replicative and transcriptional stress caused by CisPt treatment as well as interference with mechanisms of DDR and DNA repair, eventually promoting apoptosis. Thus, epigenetic targeting of DDR-related death pathways by class I HDACi is useful to overcome acquired CisPt resistance of tumor cells.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120018"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564322","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":"USP15 promotes brain cell disulfidptosis in mouse subjected to ischemic stroke through a mechanism involving deubiquitination of SETD1B","authors":"Hong-Rui Liu ,&nbsp;Lin Wu ,&nbsp;Kai-Jia Wang ,&nbsp;Yan-Xi Che ,&nbsp;Wen-Jun Zhu ,&nbsp;Xi-Sheng Li ,&nbsp;Yu Han ,&nbsp;Guang-Rong Wei ,&nbsp;Yi-Yue Zhang ,&nbsp;Xiu-Ju Luo","doi":"10.1016/j.bbamcr.2025.120016","DOIUrl":"10.1016/j.bbamcr.2025.120016","url":null,"abstract":"<div><div>Disulfidptosis due to excessive accumulation of disulfides is a novel form of regulated cell death. Whether disulfidptosis occurs in ischemic stroke and the underlying mechanisms remain elusive. RNA transcriptomics sequencing (RNA-seq) reveales that knockdown of SET domain containing 1B (SETD1B), a histone lysine methyltransferase, decreases the expression of disulfidptosis-related genes. Using Ubibrowser database, Ubiquitin-specific protease 15 (USP15) is predicted to be a deubiquitinase (DUB) for SETD1B. This study investigates whether SETD1B promote disulfidptosis in ischemic stroke via upregulating disulfidptosis-related genes and whether USP15 deubiquitinates SETD1B. A C57BL/6 J mouse model of ischemic stroke was established, which results in brain injury and upregulation of USP15 and SETD1B, concomitant with the increased disulfidptosis, as indicated by the increased level of NADP⁺/NADPH ratio, elevated protein levels of NCK associated protein 1 like (NCKAP1L) and WASP family protein member 2 (WAVE-2), disulfide bond accumulation, and cytoskeleton detachment from the cytoplasmic membrane. Similar results were observed in cultured HT22 cells subjected to oxygen-glucose deprivation plus reoxygenation (OGD/R), and USP15 or SETD1B siRNAs reversed these phenomena. Mechanistically, knockdown of SETD1B prevented H3K4me3 enrichment at the <em>Nckap1l</em> and <em>Wasf2</em> promoters and reduced <em>Nckap1l</em> and <em>Wasf2</em> expression. Moreover, knockdown of USP15 increased the ubiquitination level of SETD1B thus decreasing its protein level. Based on these findings, we concluded that SETD1B can promote disulfidptosis in stroke brain cells via a mechanism involving facilitating H3K4me3 enrichment at the <em>Nckap1l</em> and <em>Wasf2</em> promoters, while USP15 is able to deubiquitinate SETD1B and increase SETD1B level in ischemic stroke mice.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120016"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534744","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":"GlycoRNA-L and glycoRNA-S mediate human monocyte adhesion via binding to Siglec-5","authors":"Yong Li ,&nbsp;Yisong Qian ,&nbsp;Evan Huang ,&nbsp;Zain Schwarz ,&nbsp;Hannah Tai ,&nbsp;Katherine Tillock ,&nbsp;Tianhua Lei ,&nbsp;Xiaofeng Yang ,&nbsp;Mingui Fu","doi":"10.1016/j.bbamcr.2025.120017","DOIUrl":"10.1016/j.bbamcr.2025.120017","url":null,"abstract":"<div><div>It was recently reported that RNAs can be glycosylated, <em>and</em> such glycosylated RNAs (referred to as glycoRNAs) are located on the outer cell surface. We here reported that there are two forms of glycoRNAs, named as glycoRNA-L and glycoRNA-S, robustly expressed in human monocytes. We verified that the glycoRNA-S specifically detected in human monocytes is synthesized by enzyme-catalyzed conjugation, but not artificial products of labelling probe. RNase-treatment removed both glycoRNA-L and glycoRNA-S, suggesting that they are localized on cell surface. Removing glycoRNAs significantly suppressed the interaction of human monocytes with endothelial cells, suggesting that glycoRNAs mediate human monocyte adhesion. Using flow cytometry, immunoprecipitation and northern blotting we identified Siglec-5 as the binding receptor of glycoRNAs. Siglec-5 is expressed in human endothelial cells but presented on endothelial cell surface when endothelial cells are activated. We observed that glycoRNA-L was heavily labeled with sialic acid, whereas glycoRNA-S was heavily labeled with <em>N</em>-acetylgalactosamine and <em>N</em>-acetylglucosamine. Together, these results demonstrate that two forms of glycoRNAs exist in human monocytes, which may play significant role in controlling the interaction of human monocytes and endothelial cells and contribute to the pathogenesis of inflammatory diseases.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120017"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534745","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":"Mitochondrial DNA genotypes modify m.3243A>G-associated mitochondrial disease via the 15-HETE/Akt/FoxO1 pathway","authors":"Qian Wang ,&nbsp;Chang You ,&nbsp;Xiaoning Qu ,&nbsp;YiQing Zhang ,&nbsp;Yuxiao Bai ,&nbsp;Xianlong Lin ,&nbsp;Zhaoxia Wang ,&nbsp;Hezhi Fang ,&nbsp;Jianxin Lyu ,&nbsp;Minghua Jiang ,&nbsp;Ya Wang","doi":"10.1016/j.bbamcr.2025.120012","DOIUrl":"10.1016/j.bbamcr.2025.120012","url":null,"abstract":"<div><div>Mitochondrial disease caused by mitochondrial DNA (mtDNA) 3243A&gt;G mutation is characterized by high levels of clinical heterogeneity. Varied m.3243A&gt;G mutation loads among patients are used to, but cannot fully explain, disease heterogeneity. Here, we found that mtDNA genotypes (haplogroups) modify m.3243A&gt;G-associated natural selection and cell fate determination. mtDNA haplogroup M7 was less prevalent in a multi-center m.3243A&gt;G disease cohort. Further functional studies using cybrids showed that M7 accelerated cell proliferation and shortened G0/G1 cell cycle when compared with cybrid carrying a non-M7 haplogroup (D5). However, mitochondrial function and cell viability were even worse in M7 cybrid than D5 cybrid when treated with mitochondrial oxidative phosphorylation (OXPHOS) inhibitors, indicating that M7 drives negative selection in patients with m.3243A&gt;G during evolution. By adopting multi-omics strategies, we showed a lesser increase of 15-hydroxyeicosatetraenoic acid (15-HETE) levels in M7 cybrid owing to OXPHOS inhibition, leading to insufficient Akt/FoxO1 activation and increased apoptosis. Notably, 15-HETE administration activated Akt/FoxO1 phosphorylation and abolished apoptosis difference between M7 and D5 cybrids, suggesting that augmented 15-HETE was vital to protect cells from death. Collectively, our work identified a genetic modifier of m.3243A&gt;G-associated mitochondrial disease and demonstrated that the mitochondrial retrograde 15-HETE/Akt/FOXO1 signaling cascade plays an important role in protecting cells from OXPHOS dysfunction-induced cell death.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120012"},"PeriodicalIF":4.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551834","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":"Carcinoma-associated fibroblast-derived exosomes lncRNA RORA-AS1 facilitates radiotherapy resistance of oral squamous cell carcinoma through the IFITM1/STAT axis","authors":"Lei Li ,&nbsp;Peijing Ye ,&nbsp;Guoping Li,&nbsp;Tao Xie,&nbsp;Chengpeng Zha,&nbsp;Zaihui Wang,&nbsp;Dongyan He,&nbsp;Chuanzheng Sun","doi":"10.1016/j.bbamcr.2025.120015","DOIUrl":"10.1016/j.bbamcr.2025.120015","url":null,"abstract":"<div><div>We previously identified differentially expressed lncRNAs in carcinoma-associated fibroblasts (CAFs) using a lncRNA Chip. However, the molecular mechanisms by which CAFs-derived lncRNAs regulate radiotherapy resistance in Oral squamous cell carcinoma (OSCC) remain poorly understood. This study found that lncRNA RORA-AS1 (RORA-AS1) was markedly overexpressed in CAFs, exosomes derived from CAFs (CAFs-exo), and OSCC tissues. Notably, a RORA-AS1-based nomogram demonstrated robust predictive performance for OSCC patient survival. Moreover, RORA-AS1 showed a significant positive correlation with CAF infiltration. In in vitro experiments, both CAFs-CM and CAFs-exo enhanced Cal27 cell proliferation and upregulated RORA-AS1 and IFITM1 expression, while concurrently inhibiting apoptosis, upon exposure to 8 Gy X-rays irradiation. RORA-AS1 Knockdown mitigated the radiotherapy resistance induced by CAFs-exo in Cal27 cells. Mechanistically, RORA-AS1 knockdown led to increased expression of p-STAT1, p21, and p53, alongside decreased levels of p-STAT3 and IFITM1 in Cal27 cells. RIP assay confirmed the physical association between RORA-AS1 and the IFITM1 RNA complex. In in vivo experiments, CAFs-exo enhanced tumor growth and RORA-AS1 and IFITM1 expression under radiotherapy conditions, which was mitigated by RORA-AS1 knockdown. In conclusion, CAF-derived exosome RORA-AS1 facilitates radiotherapy resistance in OSCC by activating the IFITM1/STAT signaling cascade. These findings identify RORA-AS1 as a potential biomarker for the diagnosis and treatment of OSCC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120015"},"PeriodicalIF":4.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526317","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":"AAV9-mediated gene therapy restores liver function in the MEGDHEL mouse model","authors":"Ting Wei ,&nbsp;Yuyan Lin ,&nbsp;Wenhui Ouyang ,&nbsp;Yu Lei ,&nbsp;Xiali Yang ,&nbsp;Linjie Chen ,&nbsp;Xiaobai He ,&nbsp;Quan Fang ,&nbsp;Xiaoguang Zheng ,&nbsp;Hang Tong ,&nbsp;Binggang Tu ,&nbsp;Jia Zeng ,&nbsp;Jianxin Lyu ,&nbsp;Miaomiao Du ,&nbsp;Shanying Gui","doi":"10.1016/j.bbamcr.2025.120014","DOIUrl":"10.1016/j.bbamcr.2025.120014","url":null,"abstract":"<div><div>MEGDHEL syndrome is a severe mitochondrial disorder caused by mutations in the <em>SERAC1</em> gene, characterized by sensorineural deafness, encephalopathy, hepatopathy, and Leigh-like syndrome. A hallmark feature is neonatal liver failure, often leading to high mortality. There is currently no effective treatment. In this study, we used AAV9-SERAC1 gene therapy to address liver dysfunction and mitochondrial impairments in the <em>Serac1</em>^<em>−</em><em>/</em>^<em>−</em> mouse model. Treatment with 4 × 10¹¹ viral genomes led to improvements in liver histology, including reduced fatty degeneration and cholesterol accumulation, as well as enhanced mitochondrial morphology and function. Transmission electron microscopy revealed restored mitochondrial cristae and an increased number of mitochondria in treated mice. Respiratory complex showed activity recovery and mitochondrial DNA content was increased. Behavioral assessments also demonstrated significant improvements in motor coordination, with treated mice showing enhanced grasping strength and balance compared to controls. These findings suggest that AAV9-SERAC1 gene therapy can improve liver function and locomotor abilities in <em>Serac1</em>^<em>−</em><em>/</em>^<em>−</em> mice, offering a promising therapeutic strategy for MEGDHEL syndrome.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120014"},"PeriodicalIF":4.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526316","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":"Are connexin hemichannels playing any role in cancer?","authors":"Andrés Tittarelli ,&nbsp;Kevin Calderón ,&nbsp;María de los Ángeles Esveile ,&nbsp;Antonia B. Abusleme ,&nbsp;Mariana P. Arbat ,&nbsp;Mauricio A. Retamal","doi":"10.1016/j.bbamcr.2025.120013","DOIUrl":"10.1016/j.bbamcr.2025.120013","url":null,"abstract":"<div><div>Connexin (Cx) hemichannels have emerged as key regulators of both physiological and pathological processes. They exhibit a dual role in cellular function: while low-to-moderate activity supports cell-to-cell communication, excessive hemichannel opening can be detrimental, leading to cell death. In the context of cancer, the contribution of Cx hemichannels remains poorly defined. However, evidence from various models suggests that their activity may critically influence cancer progression. For example, Cx hemichannels mediate the release of signaling molecules such as ATP, which, upon conversion to adenosine, contributes to immunosuppression within the tumor microenvironment (TME). Notably, the activity of Cx hemichannels is modulated by several intracellular and extracellular factors—many of which are disrupted in tumors—suggesting that their regulatory dynamics in cancer may differ substantially from those under homeostatic conditions. This review aims to explore the potential roles of Cx hemichannels in shaping the TME, promoting immune evasion, and facilitating tumor progression. Given their putative relevance, future studies should focus on elucidating how cancer-associated alterations in regulatory mechanisms affect Cx hemichannel activity and whether such activity contributes to tumor aggressiveness. A clearer understanding of these processes may uncover novel therapeutic opportunities targeting Cx hemichannel regulation in oncology.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120013"},"PeriodicalIF":4.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513555","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}