Cellular and Molecular Life Sciences最新文献

{"title":"Mechanisms and strategies of host xenophagy manipulation by intracellular bacteria.","authors":"Yinjuan Song, Li Tang, Na Li, Xiangmei Zhou, Yuefeng Chu","doi":"10.1007/s00018-026-06323-w","DOIUrl":"10.1007/s00018-026-06323-w","url":null,"abstract":"<p><p>Xenophagy, a specialized form of autophagy, serves as a critical cellular defense mechanism, targeting and degrading intracellular bacterial pathogens. This review explores the intricate interplay between bacteria and host xenophagy, focusing on the mechanisms that underlie xenophagic recognition, encapsulation, and degradation of bacterial invaders. Despite xenophagy's essential role in host immunity, many bacteria have evolved sophisticated strategies to evade, inhibit, or even subvert this process, ensuring their survival within host cells. We provide an in-depth analysis of the bacterial mechanisms that counteract xenophagy, detailing how specific pathogens manipulate autophagosome formation, acidification, and autophagosome-lysosome fusion. Furthermore, we highlight outstanding research questions, including the mechanisms of autophagosome formation at the bacterial surface, the interaction between xenophagy and the immune system, and the impact of xenophagy on bacterial antibiotic resistance. By examining the evolving understanding of xenophagy and bacterial countermeasures, this review underscores the potential for therapeutic strategies targeting xenophagy to enhance host defense against persistent intracellular bacterial infections.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403772","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":"Retina-specific long non-coding RNAs associated with inherited retinal disease genes.","authors":"Emma Delanote, Karla Alejandra Ruiz-Ceja, Alfredo Dueñas Rey, Dalila Capasso, Manon Bouckaert, Martina Sofia, Martina Di Guida, Mario Failli, Victor López Soriano, Hanne Lenaerts, Kelly Lemeire, Birthe Dorgau, Jasper Verwilt, Sarah De Keulenaer, Filip Van Nieuwerburgh, Manon Huizing, Sarah Glorieux, Pieter-Jan Volders, Eva D'haene, Elfride De Baere, Majlinda Lako, Katrien Remaut, Nicolina Cristina Sorrentino, Pieter Mestdagh, Diego di Bernardo, Steve Lefever, Frauke Coppieters, Sandro Banfi","doi":"10.1007/s00018-026-06259-1","DOIUrl":"10.1007/s00018-026-06259-1","url":null,"abstract":"<p><p>Long non‑coding RNAs (lncRNAs) are increasingly recognized as important regulatory molecules, yet their roles remain largely unexplored in many tissues. This study aimed to identify and characterize lncRNAs involved in human retinal biology and inherited retinal disease (IRD), a leading cause of blindness worldwide. By integrating retinal tissue-specificity, location in IRD gene topologically associating domains (TADs), and co-expression analyses, we identified a set of 126 lncRNAs that are potentially regulating IRD genes. In-depth characterization of eleven selected lncRNAs, one of which is novel (LINC03128), allowed us to dissect their transcriptional units and cell type-specific expression, and revealed significant associations with visual function. Furthermore, knockdown of LINC03127 in human retinal explants and retinal organoids resulted in marked downregulation of photoreceptor-related gene pathways and pointed to a potential regulatory interaction with ABCA4, a major IRD gene located in cis. Collectively, our study provides the first systematic assessment of lncRNAs in the human retina and establishes a comprehensive resource of candidate regulatory lncRNAs with potential relevance to retinal function and disease.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403727","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":"RBMX promotes colorectal liver metastasis by stabilizing MTHFD2 mRNA to regulate redox homeostasis.","authors":"Chengrong Jiang, Guanyi Liao, Qingling Li, Kun Yang, Tao Guo, Suhe Lai, Hong Peng, Jie Hu, Minli Yang, Jinjun Guo","doi":"10.1007/s00018-026-06336-5","DOIUrl":"10.1007/s00018-026-06336-5","url":null,"abstract":"<p><strong>Background: </strong>Liver metastasis is the primary cause of mortality in colorectal cancer (CRC), yet the molecular mechanisms driving colorectal liver metastasis (CRLM) remain poorly understood. This study investigates the role of RNA-binding motif protein X (RBMX) in CRLM progression and its underlying mechanisms.</p><p><strong>Methods: </strong>RBMX expression and clinical significance were analyzed in public databases (GEO, TCGA) and in-house cohorts. Metastatic function was assessed using in vitro and in vivo models. Mechanistically, RNA sequencing, RNA immunoprecipitation (RIP), and RNA pull-down assays were employed to identify downstream targets. Metabolic profiling, reactive oxygen species (ROS) quantification, and signaling pathway analyses were used to evaluate redox homeostasis.</p><p><strong>Results: </strong>RBMX was upregulated in CRLM tissues and correlated with poor prognosis. It significantly promoted CRC cells migration, invasion, and liver metastasis. Mechanistically, RBMX directly bound to and stabilized MTHFD2 mRNA, increasing its protein abundance. This upregulation rewired one-carbon metabolism to boost NADPH production, effectively buffering intracellular ROS. Consequently, RBMX suppressed ROS-dependent p38/JNK stress signaling, sustaining metastatic cell survival.</p><p><strong>Conclusions: </strong>Our study reveals that RBMX drives CRLM by stabilizing MTHFD2 mRNA to maintain redox homeostasis. This \"RBMX-MTHFD2-Redox\" axis links RNA stability to metabolic plasticity, representing a novel mechanistic vulnerability in CRLM and promising candidate for preclinical therapeutic development and biomarker investigation.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403681","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":"From Thanatos to transcription: the emerging biology of THAP proteins.","authors":"Bryce Rampal, Alexandre Brisson, Louise Ben Hamou Kuijpers, Laurent Cappadocia, Éric Samarut","doi":"10.1007/s00018-026-06318-7","DOIUrl":"10.1007/s00018-026-06318-7","url":null,"abstract":"<p><p>The Thanatos-associated (THAP) protein family, named after the Greek god of death, comprises zinc-finger proteins characterized by a DNA-binding domain called the THAP domain. Although THAP1 and THAP11 have been extensively studied, the broader family of twelve human THAP-domain containing proteins is increasingly recognized as an important but underexplored group of transcriptional regulators. Evidence now links THAP proteins to a wide range of cellular processes, including cell-cycle progression, DNA repair, apoptosis, proteostasis, and mitochondrial function. Dysregulation of these proteins has also been implicated in cancer and neurological disorders, underscoring their medical relevance. In this review, we summarize current knowledge of their structure, localization, transcriptional roles, and disease associations. We also present new structural analyses that shed light on conserved and divergent features across the THAP family. Finally, we will highlight their newly appreciated functions in stem and progenitor cell biology.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403736","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":"Elektra-Qki and Alien-Wt1 lncRNA-protein interaction controls myocardial ion channel expression and epicardial EMT during heart development in mice.","authors":"Sheila Caño-Carrillo, Estefanía Lozano-Velasco, Diego Franco","doi":"10.1007/s00018-026-06322-x","DOIUrl":"10.1007/s00018-026-06322-x","url":null,"abstract":"<p><strong>Background: </strong>The heart is the first organ to develop during embryogenesis and its development relies on coordinated interactions between the myocardium and the embryonic epicardium (EE), the third layer of the heart derived from the proepicardium (PE). A subset of epicardial cells undergoes an epithelial-to-mesenchymal transition (EMT), invades the subepicardial space and leads to epicardial-derived cells (EPDCs) colonizing the embryonic myocardium and differentiating into multiple cardiac lineages. However, the regulatory landscape governing these processes remains incomplete. In recent years, long non-coding RNAs (lncRNAs) have emerged as key regulators of cardiac development. Previous data from our laboratory identified two murine lncRNAs, Elektra and Alien, with differential expression during the transition from the PE to the EE.</p><p><strong>Methods: </strong>In this study, we performed a multi-omic characterization of both lncRNAs across embryonic and adult tissues. Their transcriptional regulation was evaluated through cardiogenic transcription factors analysis, while their molecular interactomes were identified via RNA pull-down (PD) and mass spectrometry (MS) assays and subsequently validated by RNA immunoprecipitation (RIP). Functional impact was analyzed through loss-of-function experiments and RT-qPCR, focusing on cell migration and EMT dynamics, evidencing distinct roles for each lncRNA.</p><p><strong>Results: </strong>Elektra regulated the expression of ion channel genes in the myocardium through interaction with Qki protein, while Alien modulates the epicardial EMT process by interacting with Wt1 and controlling EMT-related genes, including Snai1, Snai2, Cdh1 and Cdh2.</p><p><strong>Conclusion: </strong>Altogether, our findings reveal that Elektra and Alien exert important roles in cardiac development by regulating myocardial ion channel expression and epicardial EMT, respectively, supporting new insights into lncRNA-mediated regulation of heart morphogenesis in mice.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396020","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":"SHIP1 is required for T cell surveillance of occult malignancies.","authors":"S Fernandes, N Srivastava, C Pedicone, R Sudan, R W Engelman, W G Kerr","doi":"10.1007/s00018-026-06326-7","DOIUrl":"10.1007/s00018-026-06326-7","url":null,"abstract":"<p><p>SHIP1-deficient mice develop severe, transmural Crohn's-like ileitis and die prematurely. Recent analysis of a human Crohn's disease (CD) cohort revealed a significant subset of patients have severely reduced levels of SHIP1 expression suggesting SHIP1 deficiency leads to CD in both rodents and humans. The mucosal inflammatory disease that causes the premature death of SHIP1^-/- mice is a consequence of the requirement of SHIP1 expression for the survival of effector T cells in mucosal tissues. T cell specific ablation of SHIP1 expression in CD4CreSHIP1^flox/flox mice also results in Crohn's disease-like ileitis, but less severe than in their germline SHIP1^-/- counterparts due to the absence of a SHIP1 deficient neutrophil compartment. Consequently CD4CreSHIP1^flox/flox mice live much longer than their SHIP1^-/- counterparts. As Crohn's disease is associated with an increased risk of intestinal cancers in humans and that T cells are proposed to protect from occult malignancies, we hypothesized that CD4CreSHIP1^flox/flox mice would develop malignancies originating in the gut. Here we show that CD4CreSHIP1^flox/flox mice with ileitis develop spontaneous metastatic cancer originating in the small intestine, including widely disseminated histiocytic sarcoma and intestinal adenocarcinomas. Our findings demonstrate that T cells in the gut are essential to protect against occult intestinal cancers and that SHIP1 is essential for this function. These findings may aid our understanding of the increased susceptibility to intestinal cancer in IBD patients, and particularly since a significant subset of adult IBD patients have defective expression of SHIP1.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396071","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":"Reply to: Commentary on \"The food additive 4-hexylresorcinol impairs intestinal stem cell function and exacerbates inflammatory bowel disease in Drosophila melanogaster via suppression of MAPK signaling pathway\".","authors":"Xinxin Fan, Jinhua Yan, Yu Yuan, Yi Chen, Haiyang Chen","doi":"10.1007/s00018-026-06277-z","DOIUrl":"10.1007/s00018-026-06277-z","url":null,"abstract":"","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":"83 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396024","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":"UBE2L6 promotes invasion and metastasis of triple-negative breast cancer by enhancing autophagy through STK38 ISGylation.","authors":"Liang Ji, Kang Li, Jing Feng, Jun-Hui Yin, Yu-Ting He, Wen-Jing Zhang, Zhuo-Ling Li, Zi-Hao Gu, Na-Min Yang, Yuan-Qi Qiao, Ren-Jie Cheng, Min Wang, Chang Liu, Xin Hai, Yi Zhou","doi":"10.1007/s00018-026-06327-6","DOIUrl":"10.1007/s00018-026-06327-6","url":null,"abstract":"<p><p>Although aberrant activation of autophagy is well known in triple-negative breast cancer (TNBC), its functional roles and underlying mechanisms remain largely unknown. In the present study, we found that high UBE2L6 expression was strongly associated with aggressive clinical features in TNBC. We demonstrated that UBE2L6 promoted migration, invasion, and lung metastasis of TNBC by enhancing STK38-mediated autophagy. Mechanistically, UBE2L6 stabilized STK38 by promoting its ISGylation and inhibiting its ubiquitin-proteasomal degradation. Therefore, targeting UBE2L6 and modulating the STK38 ISGylation-autophagy axis represent potential intervention points in TNBC.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The BmCPV-derived viral small peptide vsp1S4(-) suppresses viral replication by triggering apoptosis via the ROS-JNK signalling pathway.","authors":"Xialing Chen, Xiaoyan Du, Lixuan Li, Yao Yao, Qian Teng, Haoni Xue, Min Zhu, Xing Zhang, Chengliang Gong, Xiaolong Hu","doi":"10.1007/s00018-026-06230-0","DOIUrl":"10.1007/s00018-026-06230-0","url":null,"abstract":"<p><p>Viral antisense RNAs are generally considered noncoding. Here, we show that segment 4 of Bombyx mori cypovirus (BmCPV) encodes a 78-aa antisense-microprotein, vsp1S4(-), that triggers a host-restrictive reactive oxygen species (ROS)-c-Jun N-terminal kinase (JNK)-apoptosis axis. vsp1S4(-) localizes to mitochondria, induces superoxide release, and activates JNK signalling. Consequently, cells undergo caspase-3-dependent apoptosis and S-phase arrest, while the levels of the viral structural protein (VP7) and progeny virions are strongly suppressed. Pharmacologic interruption of either ROS with N-acetylcysteine (NAC) or JNK signalling with SP600125, a dominant-negative JNK effectively rescues VP7 expression and restores viral replication, confirming that vsp1S4(-)-elicited signalling shows antiviral activity. Thus, BmCPV autonomously limits its own propagation through an antisense-encoded peptide that weaponizes host mitochondrial ROS and JNK, representing a paradigm of programmed self-attenuation operating via antisense translation.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389776","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":"Inhibition of ferroptosis via SLC25A39-NRF2 axis drives Osimertinib resistance in lung adenocarcinoma.","authors":"Kai Fu, Zhilin Zeng, Wenfeng Wang, Wei Wu, Yijie Gong, Xiangning Fu, Yixin Cai, Changyu Liu","doi":"10.1007/s00018-026-06313-y","DOIUrl":"10.1007/s00018-026-06313-y","url":null,"abstract":"<p><strong>Objective: </strong>Overcoming resistance to Osimertinib remains a major clinical challenge in lung adenocarcinoma (LUAD). The molecular mechanisms driving this resistance are still not fully understood.</p><p><strong>Methods: </strong>Integrated bioinformatics analysis and functional assays were performed to investigate the role of SLC25A39 in LUAD progression and drug resistance. Mechanistic studies were conducted using co-immunoprecipitation and rescue experiments. Osimertinib-resistant cell models and xenograft assays were used to evaluate therapeutic responses.</p><p><strong>Results: </strong>SLC25A39 was significantly upregulated in LUAD and correlated with unfavorable patient outcomes. Functional studies showed that SLC25A39 depletion suppressed malignant phenotypes and enhanced ferroptosis, whereas its overexpression produced the opposite effects. Mechanistically, SLC25A39 was found to interact with NRF2 and was associated with increased NRF2 stability and transcriptional activity, leading to enhanced glutathione synthesis and attenuation of lipid peroxidation. Importantly, silencing SLC25A39 sensitized LUAD cells to Osimertinib. Consistent with this, pharmacological induction of ferroptosis using RSL3 markedly enhanced the antitumor effects of Osimertinib in both parental and resistant models, resulting in reduced tumor growth in vitro and in vivo, particularly in SLC25A39-high contexts.</p><p><strong>Conclusion: </strong>SLC25A39 promotes LUAD progression and Osimertinib resistance by suppressing ferroptosis via NRF2. Targeting ferroptosis may represent a promising strategy to overcome Osimertinib resistance.</p>","PeriodicalId":10007,"journal":{"name":"Cellular and Molecular Life Sciences","volume":" ","pages":""},"PeriodicalIF":6.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389797","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}