Apoptosis最新文献

{"title":"Celecoxib potentiates ribociclib-induced apoptosis and anti-tumor activity by co-targeting COX-2/NF-κB and PI3K/AKT/mTOR pathways in hormone receptor-positive/HER2-negative breast cancer","authors":"Sanghee Han,&nbsp;Hail Kim,&nbsp;Minji Choi,&nbsp;Bo-Hyung Kim,&nbsp;Sumin Chae,&nbsp;Seok-Geun Lee","doi":"10.1007/s10495-026-02340-z","DOIUrl":"10.1007/s10495-026-02340-z","url":null,"abstract":"<div>\u0000 \u0000 <p>Hormone receptor‐positive/HER2‐negative (HR⁺/HER2⁻) breast cancer accounts for the majority of breast tumours, and cyclin‑dependent kinase 4/6 (CDK4/6) inhibitors such as ribociclib have improved patient outcomes. However, their benefit is limited by resistance and dose‑limiting toxicities, while COX‑2-associated inflammatory signaling and downstream NF‑κB and PI3K/AKT/mTOR pathways contribute to cancer cell survival. We therefore examined whether the clinically available COX‑2 inhibitor celecoxib enhances ribociclib’s anti‑tumour activity in preclinical HR⁺/HER2⁻ models, primarily through in vitro mechanistic evaluation. HR⁺/HER2⁻ breast cancer cells were treated with celecoxib, ribociclib or both, and cell viability, clonogenic growth, cell‑cycle distribution and apoptosis were assessed alongside RT‑qPCR and western blotting. Drug interactions were analyzed using Chou–Talalay synergy analysis. Celecoxib plus ribociclib significantly reduced proliferation and colony formation compared with single agents and yielded combination index values &lt; 1 in multiple dose pairs, indicating synergy. The combination increased sub-G₁ and Annexin V-positive cells, reduced mRNA levels of <i>CDK1</i>, <i>CDK6</i>, <i>CCND1</i>, <i>CCNE1/E2</i>, and <i>CDC25A</i>, and lowered p-Rb, cyclin D1, CDK4, CDK1, and E2F1 protein expression. BAX increased and BCL-2 decreased. <i>IL1B</i>, <i>IL6</i>, and <i>TNF</i> transcripts, p-p65, COX-2, p-PI3K, p-AKT, and p-mTOR were also reduced. In an orthotopic MCF7 xenograft model, combined treatment was associated with greater tumour growth suppression and lower Ki‑67, p‑Rb, COX‑2 and p‑AKT expression than monotherapy, without additional toxicity under the experimental conditions tested. These findings show that celecoxib is associated with enhanced ribociclib‑induced apoptosis and anti‑tumour activity, accompanied by coordinated modulation of cell-cycle, apoptotic, inflammatory, and survival pathways. To our knowledge, this is the first report of a celecoxib–CDK4/6 inhibitor combination in HR⁺/HER2⁻ breast cancer, providing a mechanistic basis for further evaluation in more biologically robust preclinical models.</p>\u0000 </div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 5","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760446","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":"HMGB1 blockade attenuates cardiac injury induced by radiotherapy combined with PD-1 inhibitor while maintaining the anti-tumor efficacy","authors":"Yao Liu,&nbsp;Lingfeng Liu,&nbsp;Bibo Wu,&nbsp;Jing Zhang,&nbsp;Chaofen Zhao,&nbsp;Bing Lu,&nbsp;Yinxiang Hu,&nbsp;Weiwei Ouyang,&nbsp;Zhenneng Guo,&nbsp;Rong Hu,&nbsp;Shengfa Su","doi":"10.1007/s10495-025-02215-9","DOIUrl":"10.1007/s10495-025-02215-9","url":null,"abstract":"<div><p>Radioimmunotherapy for lung cancer is effective but could cause cardiac damage. Our previous research indicated that combining radiotherapy with PD-1 inhibitors leads to myocardial injury, marked by increased HMGB1 and pyroptosis-related proteins in heart tissue. Pyroptosis, a pro-inflammatory form of programmed death, releases abundant inflammatory cytokines that further amplify tissue damage. Notably, in addition to its pivotal role in cardiac injury, HMGB1 exerts context-dependent, dual effects within the tumor microenvironment—either tumor-promoting or tumor-suppressive—whose net impact remains undefined. Therefore, this study proposes to specifically block HMGB1 in a lung cancer model to determine whether this intervention can suppress pyroptosis, alleviate cardiac damage, and to concurrently evaluate its potential impact on the tumor control, thereby providing a novel therapeutic strategy to mitigate the cardiotoxicity of radiation–immunotherapy. We established a cardiac injury model in tumor-bearing mice using radiation and PD-1 inhibitors to assess the impact of HMGB1 blockade on heart and tumor treatment. We evaluated cardiac injury and fibrosis with HE and Masson staining, assessed cardiac function via echocardiography and detect the level of cytokine in heart by ELISA. Lymphocyte infiltration was analyzed by flow cytometry, while immunofluorescence, immunohistochemistry, Western blotting, and PCR examined changes of HMGB1 and pyroptosis pathways. Additionally, we monitored tumor growth and necrosis following HMGB1 blockade. Recent research demonstrates that the combination of radiotherapy and PD-1 inhibitors significantly exacerbates myocardial injury compared to radiotherapy alone. This exacerbation is evidenced by elevated levels of inflammatory cytokines, including HMGB1, IL-1β, and IL-18, within the myocardium, along with increased fibrosis and pyroptosis. Additionally, there is an upregulation of the pyroptosis pathway, specifically the HMGB1-Caspase-1-GSDMD axis. The incorporation of an HMGB1 neutralizing antibody into the combined treatment regimen has been shown to down-regulate HMGB1 and proteins associated with pyroptosis, thereby substantially reducing cardiotoxicity and myocardial injury. Notably, the administration of the antibody does not compromise the anti-tumor efficacy of the combined regimen, as indicated by comparable tumor growth, necrosis levels, and peripheral blood lymphocyte distribution relative to the group receiving the combined treatment without the antibody. HMGB1 blockade attenuates cardiac injury caused by radiotherapy combined with PD-1 inhibitor while maintaining the anti-tumor efficacy. This demonstrates that in the context of tumor treatment, targeting HMGB1 represents a promising option for alleviating the cardiac damage caused by combined therapy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 6","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969768","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":"Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications","authors":"Yu-Jie Fan,&nbsp;Wei-Jia Liu,&nbsp;Chang Liu,&nbsp;Yi-Wen Zhu,&nbsp;Ti Chu,&nbsp;Hang-Shen Han,&nbsp;Dong-Dong Wu","doi":"10.1007/s10495-026-02284-4","DOIUrl":"10.1007/s10495-026-02284-4","url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer due to its strong resistance to chemotherapeutic agents that induce apoptosis. As conventional treatments gradually lose their effectiveness over time, necroptosis has become a key therapeutic target worth exploiting. Necroptosis is a regulated cell death independent of caspases. It is driven by the receptor-interacting protein kinase 1/3 (RIPK1/3) and mixed lineage kinase domain-like pseudokinase (MLKL) signaling axis. This systematic review summarizes the complex role of necroptosis in PDAC. We clarify how necroptosis can be triggered or manipulated pharmacologically, and how it can be induced by accumulating reactive oxygen species (ROS). We also critically analyze its tumor-promoting side. Persistent necroptotic signaling reshapes the tumor microenvironment (TME) by releasing damage-associated molecular patterns (DAMPs) and activating inflammatory cascades. We also highlight the growing clinical significance of necroptosis-related genes (NRGs), long non-coding RNAs (lncRNAs), and specific biomarkers such as fermitin family member 1 (FERMT1). Finally, we propose a new, context-dependent therapeutic framework. This framework proposes a combination of strategies for controlling necroptosis induction and immunomodulatory agents, offering a reasonable strategy for PDAC management.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 5","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147714862","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":"Tumor suppressor candidate 1 (TUSC1) drives oxidative phosphorylation and tumor cell death in colorectal cancer","authors":"Janvie Manhas,&nbsp;Ruchi Bhardwaj,&nbsp;Sagar Tyagi,&nbsp;Ramani Shyam Kapuganti,&nbsp;Anushree Bharadwaj,&nbsp;Jaydeep Sharma,&nbsp;Gunjan Sharma,&nbsp;Diksha Joshi,&nbsp;Ayushi Jain,&nbsp;Priyanka Mani,&nbsp;S. V. S. Deo,&nbsp;Rajinder Parshad,&nbsp;Prasenjit Das,&nbsp;Archna Singh,&nbsp;Sam J. Mathew,&nbsp;Sudip Sen,&nbsp;Jayanth Kumar Palanichamy","doi":"10.1007/s10495-026-02336-9","DOIUrl":"10.1007/s10495-026-02336-9","url":null,"abstract":"<div><p>Tumor Suppressor Candidate-1 (TUSC1), located at chromosome 9p21.2, resides within a region frequently deleted in human malignancies, yet its role in colorectal cancer (CRC) remains undefined. We investigated TUSC1 expression and function using integrated clinical, transcriptomic, metabolic, and in-vivo approaches. Immunohistochemical analysis of 145 CRC specimens revealed a significant loss of TUSC1 protein compared to normal colon, concordant with TCGA-COAD/READ RNA-Seq datasets. DepMap CRISPR fitness screens demonstrated that TUSC1 is non-essential for baseline proliferation, supporting a tumor suppressor–like profile. Lentiviral re-expression of TUSC1 in low-expressing CRC cell lines (HCT116, SW480) induced broad transcriptomic remodeling, including suppression of PI3K–Akt–mTOR signaling and stemness programs, with concomitant enrichment of oxidative phosphorylation (OXPHOS) pathways. Quantitative proteomics and phospho-western analyses confirmed attenuation of PI3K–Akt signaling. TUSC1 overexpression led to increased mitochondrial respiration, Complex I activity, and mitochondrial mass without significant changes in glycolytic flux. It also led to elevated mitochondrial ROS levels and induced G2/M arrest and apoptosis. Antioxidants partially rescued mitochondrial ROS–dependent cytotoxicity in HCT116 cells, whereas SW480 cells displayed a more limited redox rescue. TUSC1 also reduced cancer stem cell markers, impaired clonogenicity, enhanced 5-fluorouracil sensitivity, and suppressed tumor growth in xenograft models. These findings establish TUSC1 as a metabolic tumor suppressor in CRC that attenuates PI3K–Akt signaling, enhances mitochondrial oxidative metabolism, and promotes ROS-mediated tumor cell death. This study provides the first mechanistic insight into TUSC1’s function in cancer, and its restoration or therapeutic induction of oxidative metabolic stress may represent a strategy for targeting CRCs.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 5","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147714861","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 ATG14: multi-layer autophagy control and an emerging therapeutic target in cancer","authors":"Wenbo Wang,&nbsp;Chujuan Yu,&nbsp;Fulin Sun,&nbsp;Ruofeng Wang,&nbsp;Weikai Xia,&nbsp;Qinghang Song,&nbsp;Huhu Zhang,&nbsp;Zhenzhen Jia,&nbsp;Min Zhang,&nbsp;Haoran Wang,&nbsp;Zhenxiang Wang,&nbsp;Rong Fu,&nbsp;Lina Yang","doi":"10.1007/s10495-026-02302-5","DOIUrl":"10.1007/s10495-026-02302-5","url":null,"abstract":"<div><p>ATG14 (ATG14L/Barkor) is the autophagy-specific subunit of class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) and functions as a pivotal node linking autophagosome formation to autophagosome-lysosome fusion. Functionally, ATG14 regulates cell fate through multiple mechanisms. Under hypoxic or nutrient-deprived conditions, ATG14 maintains tumor cell survival and drug resistance, remodels cellular metabolism via lipophagy and mitophagy, and can either suppress or promote programmed cell death depending on the cellular context. Moreover, ATG14 plays protective roles in maintaining neuronal and hepatic homeostasis and is involved in the development of inflammatory and metabolic disorders. Here, we discuss the multi-layered regulation of ATG14, including post-translational modifications (phosphorylation, ubiquitination, palmitoylation), epitranscriptomic and non-coding RNA regulation, and competitive complex interactions, all of which fine-tune its autophagic output and functional plasticity. We further highlight the central roles of ATG14 during the autophagic process, summarize recent advances in cancer-related ATG14 research, and review ongoing drug development efforts as well as potential therapeutic strategies targeting ATG14. Our goal is to provide a comprehensive understanding of the physiological and pathological functions of ATG14 and to explore its potential as a druggable signaling hub. Given its bidirectional regulatory capacity to either suppress cytoprotective autophagy or enforce lethal autophagy-ATG14-targeted interventions must be strategically designed based on the disease stage and autophagy dependence.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 4","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715670","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":"Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics","authors":"Yang Liu,&nbsp;Qingxin Chen,&nbsp;Jiayu Xu,&nbsp;Hao Chi","doi":"10.1007/s10495-026-02298-y","DOIUrl":"10.1007/s10495-026-02298-y","url":null,"abstract":"<div><p>Lung cancer remains the leading cause of cancer‐related mortality worldwide, with an estimated 2.2 million new cases and 1.8 million deaths in 2020. Despite improvements achieved through cytotoxic chemotherapy and immune checkpoint blockade, survival outcomes for many patients remain unsatisfactory, largely due to tumour immune-evasion and resistance to immunotherapy. In this context, programmed cell death (PCD) pathways—especially apoptosis, pyroptosis, ferroptosis and necroptosis—play central roles in shaping tumour cell fate, modulating the tumour immune microenvironment, and influencing therapeutic response. Apoptosis typically proceeds via caspase-mediated dismantling and is often immune-tolerogenic, whereas pyroptosis, ferroptosis and necroptosis provoke danger signals, inflammation and potent dendritic cell and T-cell activation, thus serving as immunogenic cell death modalities. Reciprocal crosstalk between these PCD types and the immune system determines whether lung tumours remain “cold” (immune‐excluded) or become “hot” (immune‐inflamed). Importantly, targeting these classical PCD mechanisms—either alone or in combination with immunotherapy—emerges as a promising strategy to overcome immune resistance in lung cancer by converting non-responsive tumours into immune-sensitive states. This review synthesises mechanistic insights into how apoptosis, pyroptosis, ferroptosis and necroptosis regulate antitumour immunity in lung cancer and outlines therapeutic opportunities for targeting PCD to enhance immunotherapy efficacy and overcome immune-resistant phenotypes.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 4","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715705","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 GATA3-RFPL3-ASK1 axis suppresses breast cancer growth and lung metastasis","authors":"Kang Li,&nbsp;Chang Liu,&nbsp;Jun-Hui Yin,&nbsp;Yu-Ting He,&nbsp;Zhi-Zhi Xu,&nbsp;Wen-Jing Zhang,&nbsp;Jian-Qi Wang,&nbsp;Lu-Yao Hou,&nbsp;Jing Feng,&nbsp;Le-Min Lin,&nbsp;Xiu-Qing Duan,&nbsp;Yi Zhou,&nbsp;Liang Ji","doi":"10.1007/s10495-026-02335-w","DOIUrl":"10.1007/s10495-026-02335-w","url":null,"abstract":"<div><p>Despite the great improvements made in its clinical management during the past decades, breast cancer remains a challenge with considerably high morbidity and mortality. Further efforts to explore new biomarkers with promising clinical potential are still needed nowadays. Collectively, our findings reveal the GATA3-RFPL3-ASK1 axis as a novel tumor-suppressive pathway in breast cancer. Mechanistically, GATA3 transcriptionally activates RFPL3 by directly binding to its promoter. Subsequently, RFPL3 stabilizes and activates ASK1 via K63-linked polyubiquitination, which in turn activates the ASK1-JNK/p38 signaling cascade. The signaling cascade induces apoptosis. Concurrently, this signaling cascade inhibits epithelial-mesenchymal transition (EMT) and invadopodia formation, thereby effectively inhibiting cell migration and invasion. The GATA3-RFPL3-ASK1 axis suppresses breast cancer growth and lung metastasis in vivo.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 4","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715683","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":"Relationship between different modes of death and premature ovarian insufficiency: a literature review","authors":"Huihui Li,&nbsp;Ruotong Ju,&nbsp;Puhua zhang,&nbsp;Chenyu Jia,&nbsp;Tingting Xue,&nbsp;Shu Wang,&nbsp;Xinyu Zhu,&nbsp;Ruixiang Zhu,&nbsp;Jiali Luo,&nbsp;Xuan Jing,&nbsp;Xiangrong Cui","doi":"10.1007/s10495-026-02337-8","DOIUrl":"10.1007/s10495-026-02337-8","url":null,"abstract":"<div><p>Early-onset ovarian insufficiency (POI) is a heterogeneous disorder characterized by complex etiology and the involvement of diverse programmed cell death modalities. This review aims to systematically elucidate the molecular mechanisms underlying programmed cell death in the pathogenesis of POI, with an emphasis on regulatory signaling networks and the dynamic switching of cell death modalities under distinct etiological contexts. We summarize the roles of key programmed cell death pathways—including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death—in the onset and progression of POI. In addition, potential therapeutic strategies targeting dysregulated cell death processes are briefly discussed.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 4","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697433","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":"Kaempferol protects melanocytes from ferroptosis by modulating the NF-κB/PTGS2 signaling axis in vitiligo","authors":"Xuqing Xu,&nbsp;Zixian Lei,&nbsp;Wen Hu,&nbsp;Hongjuan Wang,&nbsp;Fang Xiang,&nbsp;Yuan Ding,&nbsp;Xiaojing Kang","doi":"10.1007/s10495-026-02334-x","DOIUrl":"10.1007/s10495-026-02334-x","url":null,"abstract":"<div><p>Oxidative stress-induced ferroptosis is increasingly recognized as an important contributor to melanocyte destruction in vitiligo; however, the specific upstream signaling networks linking inflammatory signaling to ferroptosis susceptibility remain incompletely defined. Kaempferol, a natural flavonoid and key bioactive constituent of the traditional herb <i>Vernonia anthelmintica</i> (L.) Willd., possesses antioxidant and anti-inflammatory properties, yet its potential to mitigate melanocyte ferroptosis warrants investigation. We established an RSL3 (Ras-selective lethal 3)-induced ferroptosis model in primary human melanocytes and employed a multi-dimensional approach integrating transcriptomic profiling, network pharmacology, molecular docking, and immunofluorescence analysis. Clinical relevance was validated using lesional skin tissues from vitiligo patients. RSL3 challenge triggered canonical ferroptosis features, including lethal lipid peroxidation, glutathione depletion, and characteristic mitochondrial shrinkage, all of which were significantly attenuated by kaempferol. Mechanistically, unbiased transcriptomic and network analyses identified prostaglandin-endoperoxide synthase 2 (PTGS2) as a convergent node associated with both nuclear factor-κB (NF-κB)-driven inflammatory signaling and ferroptosis stress. We found that kaempferol markedly inhibited p65 nuclear translocation, accompanied by suppression of PTGS2 transcription. Notably, pharmacological inhibition of NF-κB using BAY 11-7082 phenocopied the anti-ferroptosis efficacy of kaempferol, supporting the functional involvement of this signaling axis. Furthermore, clinical analyses revealed aberrant activation of the NF-κB/PTGS2 pathway concomitant with ferroptosis signatures in vitiligo lesions. Our findings identify ferroptosis as a critical mechanism of melanocyte injury and delineate an NF-κB/PTGS2-associated signaling framework linking oxidative stress, inflammatory activation, and ferroptosis damage. By modulating this stress-responsive axis, kaempferol confers robust protection against ferroptosis melanocyte injury, highlighting its potential relevance as a ferroptosis-modulating strategy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 4","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687663","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":"Dynamic collaboration between mitochondria and organelles: mechanisms, functions, and disease implications","authors":"Bin Shao,&nbsp;Yifeng Zeng,&nbsp;Jian Ju","doi":"10.1007/s10495-026-02338-7","DOIUrl":"10.1007/s10495-026-02338-7","url":null,"abstract":"<div><p>In recent years, numerous studies have revealed that dysregulation of mitochondria-organelle interactions is a common feature underlying various pathological processes and pathogen infections. For instance, in Alzheimer's disease (AD), dysfunction of mitochondrial-associated ER membranes (MAMs) leads to calcium overload and oxidative stress, while cancer cells enhance glycolysis by remodeling mitochondria-Golgi interactions. Targeting these key interacting nodes has shown significant therapeutic potential. Although technological advances have uncovered some underlying mechanisms, the spatiotemporal dynamics, tissue specificity, and causal role of organelle interactions in diseases remain unclear. In-depth understanding of these collaborative networks will provide new targets for the treatment of cancer, metabolic syndrome, and neurodegenerative diseases, and also create novel possibilities for elucidating pathogen-host interaction mechanisms and developing anti-infective therapies. Given the importance of dynamic mitochondria-organelle collaboration in disease treatment, this review first focuses on analyzing the molecular mechanisms underlying this crosstalk. Building on this, the dysregulation of mitochondria-organelle collaboration in diseases is discussed in depth, with a particular focus on cancer, cardiovascular diseases, metabolic syndrome, and neurodegenerative diseases. Finally, the potential therapeutic strategies targeting organelle interactions are summarized and analyzed. In conclusion, the information in this manuscript offers a new way to think about and treat several serious illnesses.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 4","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687716","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}