Cell Death & Disease最新文献

{"title":"β-Hydroxybutyrate suppresses M1 macrophage polarization through β-hydroxybutyrylation of the STAT1 protein.","authors":"Ya-Ping Bai, Yu-Jie Xing, Tao Ma, Kai Li, Teng Zhang, De-Guo Wang, Shu-Jun Wan, Cui-Wei Zhang, Yue Sun, Meng-Yan Wang, Guo-Dong Wang, Wen-Jun Pei, Kun Lv, Yan Zhang, Xiang Kong","doi":"10.1038/s41419-024-07268-3","DOIUrl":"10.1038/s41419-024-07268-3","url":null,"abstract":"<p><p>β-Hydroxybutyrate (β-OHB), the primary ketone body, is a bioactive metabolite that acts as both an energy substrate and a signaling molecule. Recent studies found that β-OHB inhibits the production of pro-inflammatory cytokines in macrophages, but its underlying molecular mechanisms have not yet been fully elucidated. Lysine β-hydroxybutyrylation (Kbhb), a post-translational modification mediated by β-OHB, plays a key role in regulating the expression and activity of modified proteins. However, whether macrophages undergo protein Kbhb and whether Kbhb modification regulates macrophage polarization remains largely unknown. In this study, treatment with β-OHB and ketone ester significantly decreased the lipopolysaccharide (LPS)-induced enhancement of the M1 phenotype of mouse bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and peritoneal macrophages (PMs) in vitro and in vivo. Moreover, β-OHB treatment induced global protein Kbhb, which is associated with the regulation of macrophage M1 polarization. Proteome-wide Kbhb analysis in β-OHB-treated BMDMs revealed 3469 Kbhb modification sites within 1549 proteins, among which interleukin-12-responding proteins were significantly upregulated. Our results indicated that β-OHB regulated M1 macrophage polarization by inducing Kbhb modification of the signal transducer and activator of transcription 1 (STAT1) K679 site, which inhibited its LPS-induced phosphorylation and transcription. Altogether, our study demonstrated the presence of a widespread Kbhb landscape in the β-OHB-treated macrophages and provided novel insights into the anti-inflammatory effects of β-OHB.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 12","pages":"874"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 USP11/Nrf2 positive feedback loop promotes colorectal cancer progression by inhibiting mitochondrial apoptosis.","authors":"Yuanyuan Lu, Wanhui Wei, Mengting Li, Danyang Chen, Wenjie Li, Qian Hu, Shouquan Dong, Lan Liu, Qiu Zhao","doi":"10.1038/s41419-024-07188-2","DOIUrl":"https://doi.org/10.1038/s41419-024-07188-2","url":null,"abstract":"<p><p>Abnormal antioxidant capacity of cancer is closely related to tumor malignancy. Modulation of oxidative stress status is a novel anticancer therapeutic target. Nrf2 is a key regulator of various antioxidant enzymes, but the mechanism of its deubiquitination remains largely unclear. This study unveiled that Nrf2 received post-transcriptional regulation from a proteasome-associated deubiquitinating enzyme, USP11, in colorectal cancer (CRC). It was found that USP11 was overexpressed in CRC tissues acting as an oncogene by inhibiting mitochondrial apoptosis, and USP11 managed to maintain balance in the production and elimination of reactive oxygen species (ROS). Mechanistically, we identified a feedback loop between USP11 and Nrf2 maintaining the redox homeostasis. USP11 stabilized Nrf2 by deubiquitinating and protecting it from proteasome-mediated degradation. Interestingly, we also map that Nrf2 could bind to the antioxidant reaction element (ARE) in the USP11 promoter to promote its transcription. Hence, USP11/Nrf2 positive feedback loop inhibited mitochondrial apoptosis of CRC cells by activating Nrf2/ARE signaling pathway, thus promoting CRC progression. Schematic diagram of the mechanism by which USP11/Nrf2 positive feedback loop inhibited mitochondrial apoptosis in CRC cells. This study found that USP11 was highly expressed in colorectal cancer (CRC) tissue and was associated with poor prognosis. In CRC, the inhibition of USP11 expression could promote the ubiquitination degradation of Nrf2, thereby inhibiting the Nrf2/ARE signaling pathway. This led to an increase in reactive oxygen species in the cell, causing mitochondrial apoptosis. In addition, Nrf2 could bind to the promoter region of USP11 to promote its transcription, both of which formed positive feedback loop.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 12","pages":"873"},"PeriodicalIF":8.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilization of SQLE mRNA by WTAP/FTO/IGF2BP3-dependent manner in HGSOC: implications for metabolism, stemness, and progression.","authors":"Rui Hou, Xinrui Sun, Shiyao Cao, Yadong Wang, Luo Jiang","doi":"10.1038/s41419-024-07257-6","DOIUrl":"https://doi.org/10.1038/s41419-024-07257-6","url":null,"abstract":"<p><p>The metabolic reprogramming in high-grade serous ovarian carcinoma (HGSOC) affects the tumor stemness, which mediates tumor recurrence and progression. Knowledge of the stemness and metabolic characteristics of HGSOC is insufficient. Squalene epoxidase (SQLE), a key enzyme in cholesterol metabolism, was significantly upregulated in HGSOC samples with a fold change of about 4 in the RNA sequencing analysis. SQLE was positively related to peritoneal metastasis and poor prognosis of HGSOC patients. Functionally, SQLE drove cancer cell proliferation and inhibited apoptosis to accelerate HGSOC growth. SQLE was highly expressed in ALDH⁺CD133⁺ FACS-sorted cells derived from HGSOC cells and ovarian cancer stem cells (OCSCs)-enriched tumorspheres. SQLE overexpression resulted in enhanced CSC-like properties, including increased tumorsphere formation and stemness markers expression. In vivo, SQLE not only promoted cell line-derived xenografts growth but extended the OCSCs subpopulation of single-cell suspension. Moreover, non-targeted metabolomics profiling from UPLC-MS/MS system identified 90 differential metabolites responding to SQLE overexpression in HGSOC cells. Among them, the dysfunctional metabolisms of cholesterol and glutathione were involved in the maintenance of HGSOC stemness. Previous studies showed the alteration of N6-Methyladenosine (m6A) modification in HGSOC development. Herein, the m6A modification in the 3'UTR and CDS regions of SQLE mRNA was increased due to upregulated methyltransferases WTAP and downregulated demethylases FTO, which was recognized by m6A-binding proteins IGF2BP3, rather than IGF2BP1 or IGF2BP2, thereby stabilizing the SQLE mRNA. These results suggested that SQLE was a novel potential clinical marker for predicting the HGSOC development and prognosis, as well as a potential therapeutic target of HGSOC.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 12","pages":"872"},"PeriodicalIF":8.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOCK8 gene mutation alters cell subsets, BCR signaling, and cell metabolism in B cells.","authors":"Heng Gu, Miaomiao Xie, Siyu Zhao, Xi Luo, Yanmei Huang, Lu Yang, Fei Guan, Jiahui Lei, Chaohong Liu","doi":"10.1038/s41419-024-07180-w","DOIUrl":"https://doi.org/10.1038/s41419-024-07180-w","url":null,"abstract":"<p><p>DOCK8 deficiency has been shown to affect the migration, function, and survival of immune cells in innate and adaptive immune responses. The immunological mechanisms underlying autosomal recessive (AR) hyper-IgE syndrome (AR-HIES) caused by DOCK8 mutations remain unclear, leading to a lack of specific therapeutic options. In this study, we used CRISPR/Cas9 technology to develop a mouse model with a specific DOCK8 point mutation in exon 45 (c.5846C>A), which is observed in patients with AR-HIES. We then investigated the effect of this mutation on B cell development, cell metabolism, and function in a mouse model with Dock8 gene mutation. The results demonstrated that Dock8 gene mutation inhibited splenic MZ and GC B cell development and crippled BCR signaling. In addition, it resulted in enhanced glycolysis in B cells. Mechanistically, the reduced BCR signaling was related to decreased B cell spreading, BCR clustering, and signalosomes, mediated by inhibited activation of WASP. Furthermore, the DOCK8 mutation led to increased expression of c-Myc in B cells, which plays an important role in glycolysis. As such, GC B cells' formation and immune responses were disturbed in LCMV-infected mice. These findings will provide new insights into the immunological pathogenesis of primary immunodeficiency disorder caused by DOCK8 mutation.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 11","pages":"871"},"PeriodicalIF":8.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High iASPP (PPP1R13L) expression is an independent predictor of adverse clinical outcome in acute myeloid leukemia (AML).","authors":"Mihada Bajrami Saipi, Alessia Ruiba, Marcus Matthias Schittenhelm, Gunnar Blumenstock, Balázs Győrffy, Serena Fazio, Marlon Hafner, Anna-Lena Ahrens, Lara Aldinger, Vanessa Aellig, François G Kavelaars, César Nombela-Arrieta, Falko Fend, Peter J M Valk, Driessen Christoph, Kerstin Maria Kampa-Schittenhelm","doi":"10.1038/s41419-024-07190-8","DOIUrl":"https://doi.org/10.1038/s41419-024-07190-8","url":null,"abstract":"<p><p>Apoptosis-stimulating proteins of p53 (ASPPs) are a family of proteins that modulate key tumor suppressor pathways via direct interaction with p53. Deregulation of these proteins promotes cancer development and impairs sensitivity to systemic (chemo)therapy and radiation. In this study, we describe that the inhibitor of ASPP (iASPP) is frequently highly expressed in acute myeloid leukemia (AML) and that overexpression correlates with a poor clinical outcome. Four independent patient cohorts comprising about 1500 patient samples were analysed and consistently confirm an association of high iASPP expression with unfavourable clinical characteristics and shorter survival. Notably, the predictive role of iASPP is independent of, and adds information to, the European LeukemiaNET (ELN) risk classification. iASPP-interference cell models were developed to investigate the underlying functional aspects of iASPP in AML biology. Attenuation of iASPP expression resulted in reduced proliferation rates of leukemic blasts and rendered cells more susceptible towards induction of apoptosis in response to cytotoxic therapy. In line, independent NSG xenograft mouse experiments demonstrate that attenuation of iASPP results in a significant delay of disease onset and tumor burden and this translates to longer overall survival of mice. In conclusion, deregulation of iASPP has direct functional consequences in AML. Determination of iASPP expression levels provides valuable additional information as a predictive marker in AML and may guide treatment decisions.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 11","pages":"869"},"PeriodicalIF":8.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GEFT inhibits the GSDM-mediated proptosis signalling pathway, promoting the progression and drug resistance of rhabdomyosarcoma.","authors":"Fan Yang, Tian Xia, Zhijuan Zhao, Jinyang Lin, Ling Zhong, Tian Tang, Degui Liao, Miaoling Lai, Jiamin Ceng, Lian Meng, Feng Li, Chunxia Liu","doi":"10.1038/s41419-024-07243-y","DOIUrl":"https://doi.org/10.1038/s41419-024-07243-y","url":null,"abstract":"<p><p>The metastasis or recurrence of rhabdomyosarcoma (RMS) is the primary cause of tumour-related deaths. Patients with high-risk RMS have poor prognosis with a 5-year overall survival rate of 20-30%. The lack of specific drug-targeted therapy and chemotherapy resistance are the main reasons for treatment failure. Drugs or molecular target inhibitors can induce the pyroptosis of tumour cells or increase their sensitivity to chemotherapy, making pyroptosis an effective strategy for antitumour therapies. Pyroptosis is mediated by gasdermin (GSDM) family members. Here, we found that the expression of NLRP3, caspase-1, caspase-3, GSDMD and GSDME in RMS was remarkably lower than that in skeletal muscle tissues. Nigericin and dactinomycin in RMS cells achieved their regulatory effect on pyroptosis through the NLRP3/caspase-1/GSDMD pathway and caspase-3/GSDME pathway, respectively. Necrosulfonamide reversed the pyroptosis-related changes induced by nigericin, and siGSDME converted the dactinomycin-induced pyroptosis into apoptosis. Additionally, GEFT inhibited the GSDMD and GSDME pyroptosis pathways, thereby promoting the progression and drug resistance of RMS. Mouse xenograft and tumour analysis confirmed that nigericin and dactinomycin can effectively improve the therapeutic effect of RMS by activating the pyroptosis pathway. To the best of our knowledge, this study was the first to focus on pyroptosis in RMS. Overall, our investigation demonstrated that nigericin and dactinomycin play therapeutic roles in tumours by promoting RMS cell pyroptosis. Interference with GEFT and drug combination can exert a great inhibitory effect on tumours.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 11","pages":"867"},"PeriodicalIF":8.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OPA1 and disease-causing mutants perturb mitochondrial nucleoid distribution.","authors":"J Macuada, I Molina-Riquelme, G Vidal, N Pérez-Bravo, C Vásquez-Trincado, G Aedo, D Lagos, P Yu-Wai-Man, R Horvath, T J Rudge, B Cartes-Saavedra, V Eisner","doi":"10.1038/s41419-024-07165-9","DOIUrl":"https://doi.org/10.1038/s41419-024-07165-9","url":null,"abstract":"<p><p>Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity. The mtDNA encodes electron transport chain subunits and is packaged into nucleoids spread within the mitochondrial population. Nucleoids interact with the IMM, and their distribution is tightly linked to mitochondrial fusion and cristae shaping. Yet, little is known about the physio-pathological relevance of nucleoid distribution. We studied the effect of OPA1 and ADOA-associated mutants on nucleoid distribution using high-resolution confocal microscopy. We applied a novel model incorporating the mitochondrial context, separating nucleoid distribution into the array in the mitochondrial population and intramitochondrial longitudinal distribution. Opa1-null cells showed decreased mtDNA levels and nucleoid abundance. Also, loss of Opa1 led to an altered distribution of nucleoids in the mitochondrial population, loss of cristae periodicity, and altered nucleoids to cristae proximity partly rescued by OPA1 isoform 1. Overexpression of WT OPA1 or ADOA-causing mutants c.870+5 G > A or c.2713 C > T in WT cells, showed perturbed nucleoid array in the mitochondria population associated with cristae disorganization, which was partly reproduced in Skeletal muscle-derived fibroblasts from ADOA patients harboring the same mutants. Opa1-null and cells overexpressing ADOA mutants accumulated mitochondria without nucleoids. Interestingly, intramitochondrial nucleoid distribution was only altered in Opa1-null cells. Altogether, our results highlight the relevance of OPA1 in nucleoid distribution in the mitochondrial landscape and at a single-organelle level and shed light on new components of ADOA etiology.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 11","pages":"870"},"PeriodicalIF":8.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A N7-methylguanosine modified circular RNA, circIPP2A2, promotes malignant behaviors in hepatocellular carcinoma by serving as a scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis.","authors":"Zeyi Guo, Zhongzhe Li, Jinhao Guo, Luxiang Gan, Haiyu Mo, Jiajun Zhang, Yu Fu, Yi Wang, Meixian Jin, Yanping Wu, Qingyu Xie, Kunjiang Tan, Chunming Wang, Yuyan Xu, Guolin He, Lei Cai, Yi Gao, Mingxin Pan, Shunjun Fu","doi":"10.1038/s41419-024-07248-7","DOIUrl":"https://doi.org/10.1038/s41419-024-07248-7","url":null,"abstract":"<p><p>Despite the advancements in treatment strategies, the long-term survival of hepatocellular carcinoma (HCC) is still pessimistic. Therefore, understanding the mechanisms of hepatocellular carcinoma may offer substantial benefits for patients. Our previous research has revealed that Hornerin promoted HCC progression by regulating the AKT signaling pathway. To investigate the upstream regulatory mechanism, the results from RNA Immunoprecipitation and RNA pull-down indicated that the specific region of circIPP2A2 interacted with Hornerin. Additionally, patients with circIPP2A2 upregulation exhibited a poorer survival outcome following surgery compared to the cases with downregulated circIPP2A2. After the structure verification of circIPP2A2, loss-of-function studies using a lentiviral vector revealed that circIPP2A2 downregulation significantly inhibited HCC tumorigenesis and progression both in vitro and in vivo. Mechanistically, the m7G-MeRIP results demonstrated significant enrichment of circIPP2A2. Subsequent studies validated that METTL1 influenced the stability of circIPP2A2 and its binding affinity with Hornerin. Immunoprecipitation and immunofluorescence indicated that circIPP2A2 served as a molecular scaffold to facilitate Hornerin to interact with PI3K. In conclusion, our findings reveal that circIPP2A2, regulated by N7-methylguanosine modification, promotes malignant behaviors in HCC by serving as a molecular scaffold in modulating the Hornerin/PI3K/AKT/GSK3β axis. Targeting circIPP2A2 may be a promising therapeutic strategy for patients with HCC.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 11","pages":"868"},"PeriodicalIF":8.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipocalin-2 promotes CKD vascular calcification by aggravating VSMCs ferroptosis through NCOA4/FTH1-mediated ferritinophagy.","authors":"Yujia Wang, Yuxia Zhang, Min Gao, Zhiqing Chen, Jing Lu, Yongqi Li, Yan Di, Yinan Zhao, Bicheng Liu, Rining Tang","doi":"10.1038/s41419-024-07260-x","DOIUrl":"10.1038/s41419-024-07260-x","url":null,"abstract":"<p><p>Vascular calcification (VC) is a common complication of chronic kidney disease (CKD), for which no effective therapies are available. Hyperphosphatemia, a feature of CKD, is a well-known inducer of VC. High phosphate (HP)-induced ferroptosis plays a crucial role in CKD-related VC (CKD-VC), but the mechanisms remain unclear. Lipocalin-2 (LCN2), an iron-trafficking protein, has been implicated in ferroptosis regulation. In the present study, the role of LCN2 as a potential mediator of CKD-VC was investigated. HP-induced LCN2 expression in the arteries of CKD-VC patients, animal models and vascular smooth muscle cells (VSMCs). LCN2 knockout (LCN2KO) mice and wild-type (WT) mice fed with a high adenine and phosphate (AP) diet were studied to explore CKD-VC. Compared with WT mice, LCN2KO mice showed an amelioration of the CKD-VC induced by the AP diet. The inhibition of LCN2 also alleviated HP-induced calcium deposition and phenotypic transition in VSMCs. Conversely, VSMCs-targeted LCN2 overexpression or recombinant LCN2 treatment exacerbated CKD-VC in vivo and in vitro. Mechanistically, nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1)-mediated ferritinophagy-dependent ferroptosis was involved in LCN2-mediated CKD-VC. Under HP conditions, LCN2 interacted with NCOA4, potentially accelerating the degradation of FTH1 and inducing ferroptosis. The inhibition of LCN2 may rescue the degradation of FTH1 and thus ameliorate ferroptosis, significantly suppressing VSMCs calcification. In summary, our study revealed a novel role for LCN2 induced ferritinophagy-dependent ferroptosis in CKD-VC, and targeting LCN2 might be a promising treatment for CKD-VC.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 11","pages":"865"},"PeriodicalIF":8.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: AnnexinA7 promotes epithelial-mesenchymal transition by interacting with Sorcin and contributes to aggressiveness in hepatocellular carcinoma.","authors":"Fei Ling, Huan Zhang, Yunliang Sun, Jinyi Meng, Jaceline Gislaine Pires Sanches, He Huang, Qingqing Zhang, Xiao Yu, Bo Wang, Li Hou, Jun Zhang","doi":"10.1038/s41419-024-07184-6","DOIUrl":"10.1038/s41419-024-07184-6","url":null,"abstract":"","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"15 11","pages":"866"},"PeriodicalIF":8.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}