Cell Death and Differentiation最新文献_第8页

ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure. ARHGAP26 缺乏会导致卵母细胞非整倍体和早期胚胎发育失败。

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-23 DOI: 10.1038/s41418-024-01384-5

Sen Li, Yu Zhang, Ruiying Yuan, Shuai Zhu, Jie Bai, Yilong Miao, Xianghong Ou, Qiang Wang, Bo Xiong

{"title":"ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure.","authors":"Sen Li, Yu Zhang, Ruiying Yuan, Shuai Zhu, Jie Bai, Yilong Miao, Xianghong Ou, Qiang Wang, Bo Xiong","doi":"10.1038/s41418-024-01384-5","DOIUrl":"10.1038/s41418-024-01384-5","url":null,"abstract":"Aneuploidy, the presence of a chromosomal anomaly, is a major cause of spontaneous abortions and recurrent pregnancy loss in humans. However, the underlying molecular mechanisms still remain poorly understood. Here, we report that ARHGAP26, a putative tumor suppressor gene, is a newly identified regulator of oocyte quality to maintain mitochondrial integrity and chromosome euploidy, thus ensuring normal embryonic development and fertility. Taking advantage of knockout mouse model, we revealed that genetic ablation of Arhgap26 caused the oocyte death at GV stage due to the mitochondrial dysfunction-induced ROS accumulation. Lack of Arhgap26 also impaired both in vitro and in vivo maturation of survived oocytes which results in maturation arrest and aneuploidy, and consequently leading to early embryonic development defects and subfertility. These observations were further verified by transcriptome analysis. Mechanistically, we discovered that Arhgap26 interacted with Cofilin1 to maintain the mitochondrial integrity by regulating Drp1 dynamics, and restoration of Arhgap26 protein level recovered the quality of Arhgap26-null oocytes. Importantly, we found an ARHGAP26 mutation in a patient with history of recurrent miscarriage by chromosomal microarray analysis. Altogether, our findings uncover a novel function of ARHGAP26 in the oocyte quality control and prevention of aneuploidy and provide a potential treatment strategy for infertile women caused by ARHGAP26 mutation.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":" ","pages":""},"PeriodicalIF":13.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury by promoting ferroptosis through disrupting NDUFA1 and FSP1 interaction IDH1-R132H 突变通过破坏 NDUFA1 和 FSP1 的相互作用促进铁变态反应，从而加重顺铂诱导的急性肾损伤

IF 12.4 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-22 DOI: 10.1038/s41418-024-01381-8

Kunmei Lai, Zhimin Chen, Siyi Lin, Keng Ye, Ying Yuan, Guoping Li, Yankun Song, Huabin Ma, Tak W. Mak, Yanfang Xu

{"title":"The IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury by promoting ferroptosis through disrupting NDUFA1 and FSP1 interaction","authors":"Kunmei Lai, Zhimin Chen, Siyi Lin, Keng Ye, Ying Yuan, Guoping Li, Yankun Song, Huabin Ma, Tak W. Mak, Yanfang Xu","doi":"10.1038/s41418-024-01381-8","DOIUrl":"https://doi.org/10.1038/s41418-024-01381-8","url":null,"abstract":"The IDH1-R132H mutation is implicated in the development of various tumors. Whether cisplatin, a common chemotherapeutic agent, induces more significant renal toxicity in individuals with the IDH1-R132H mutation remains unclear. In this study, we observed that the IDH1-R132H mutation exacerbates mitochondrial lipid peroxidation and dysfunction in renal tubules, rendering the kidneys more susceptible to cisplatin-induced ferroptosis. The IDH1-R132H mutation increases methylation of the Ndufa1 promoter, thereby suppressing NDUFA1 transcription and translation. This suppression disrupts NDUFA1’s interaction with FSP1, reducing its resistance to cisplatin-induced tubular epithelial cell death. As a consequence, ROS accumulates, lipid peroxidation occurs, and ferroptosis is triggered, thereby promoting acute kidney injury. In summary, this study elucidates a novel mechanism underlying cisplatin-induced nephrotoxicity and provides valuable insights for the development of personalized treatment strategies for tumor patients carrying the IDH1-R132H mutation.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"25 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The long non-coding RNA ROSALIND protects the mitochondrial translational machinery from oxidative damage 长非编码 RNA ROSALIND 保护线粒体翻译机制免受氧化损伤

IF 12.4 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-18 DOI: 10.1038/s41418-024-01377-4

Vicky Katopodi, Alessandro Marino, Nikoleta Pateraki, Yvessa Verheyden, Sonia Cinque, Elena Lara Jimenez, Sara Adnane, Ewout Demesmaeker, Alice Scomparin, Rita Derua, Elisabetta Groaz, Eleonora Leucci

{"title":"The long non-coding RNA ROSALIND protects the mitochondrial translational machinery from oxidative damage","authors":"Vicky Katopodi, Alessandro Marino, Nikoleta Pateraki, Yvessa Verheyden, Sonia Cinque, Elena Lara Jimenez, Sara Adnane, Ewout Demesmaeker, Alice Scomparin, Rita Derua, Elisabetta Groaz, Eleonora Leucci","doi":"10.1038/s41418-024-01377-4","DOIUrl":"https://doi.org/10.1038/s41418-024-01377-4","url":null,"abstract":"Upregulation of mitochondrial respiration coupled with high ROS-scavenging capacity is a characteristic shared by drug-tolerant cells in several cancers. As translational fidelity is essential for cell fitness, protection of the mitochondrial and cytosolic ribosomes from oxidative damage is pivotal. While mechanisms for recognising and repairing such damage exist in the cytoplasm, the corresponding process in the mitochondria remains unclear.By performing Ascorbate PEroXidase (APEX)-proximity ligation assay directed to the mitochondrial matrix followed by isolation and sequencing of RNA associated to mitochondrial proteins, we identified the nuclear-encoded lncRNA ROSALIND as an interacting partner of ribosomes. ROSALIND is upregulated in recurrent tumours and its expression can discriminate between responders and non-responders to immune checkpoint blockade in a melanoma cohort of patients. Featuring an unusually high G content, ROSALIND serves as a substrate for oxidation. Consequently, inhibiting ROSALIND leads to an increase in ROS and protein oxidation, resulting in severe mitochondrial respiration defects. This, in turn, impairs melanoma cell viability and increases immunogenicity both in vitro and ex vivo in preclinical humanised cancer models. These findings underscore the role of ROSALIND as a novel ROS buffering system, safeguarding mitochondrial translation from oxidative stress, and shed light on potential therapeutic strategies for overcoming cancer therapy resistance.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"1 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retention of ES cell-derived 129S genome drives NLRP1 hypersensitivity and transcriptional deregulation in Nlrp3tm1Flv mice 保留 ES 细胞衍生的 129S 基因组会导致 Nlrp3tm1Flv 小鼠 NLRP1 超敏和转录失调

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-17 DOI: 10.1038/s41418-024-01379-2

Felix D. Weiss, Yubell Alvarez, Farhad Shakeri, Anshupa Sahu, Petro Leka, Alesja Dernst, Jessika Rollheiser, Matilde Vasconcelos, Adriana Geraci, Fraser Duthie, Rainer Stahl, Hye Eun Lee, Anne-Kathrin Gellner, Andreas Buness, Eicke Latz, Felix Meissner

{"title":"Retention of ES cell-derived 129S genome drives NLRP1 hypersensitivity and transcriptional deregulation in Nlrp3tm1Flv mice","authors":"Felix D. Weiss, Yubell Alvarez, Farhad Shakeri, Anshupa Sahu, Petro Leka, Alesja Dernst, Jessika Rollheiser, Matilde Vasconcelos, Adriana Geraci, Fraser Duthie, Rainer Stahl, Hye Eun Lee, Anne-Kathrin Gellner, Andreas Buness, Eicke Latz, Felix Meissner","doi":"10.1038/s41418-024-01379-2","DOIUrl":"10.1038/s41418-024-01379-2","url":null,"abstract":"Immune response genes are highly polymorphic in humans and mice, with heterogeneity amongst loci driving strain-specific host defence responses. The inadvertent retention of polymorphic loci can introduce confounding phenotypes, leading to erroneous conclusions, and impeding scientific advancement. In this study, we employ a combination of RNAseq and variant calling analyses to identify a substantial region of 129S genome, including the highly polymorphic Nlrp1 locus, proximal to Nlrp3, in one of the most commonly used mouse models of NLRP3 deficiency (Nlrp3tm1Flv). We show that the presence of the Nlrp1129S locus leads to an increase in NLRP1B protein expression, and a sensitising of Nlrp3tm1Flv macrophages to NLRP1 inflammasome activation, independent of NLRP3 deficiency. Retention of 129S genome further leads to protein sequence differences and altered gene regulation across multiple cell types, including of the key tissue-resident macrophage marker, TIM4. Using alternative models of NLRP3 deficiency, including a previously undescribed conditional Nlrp3 allele enabling precise temporal and cell-type specific control over Nlrp3 deletion, we further show that NLRP3 contributes to Talabostat-driven IL-1β release. Our study also establishes a generic framework to identify functionally relevant SNPs and assess genomic contamination in transgenic mice using RNAseq data. This allows for unambiguous attribution of phenotypes to the target gene and advances the precision and reliability of research in the field of host defence responses.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"31 12","pages":"1717-1729"},"PeriodicalIF":13.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01379-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236237","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}

引用次数: 0

Feeding cancer to death - a triad of aromatic acids reduces tumor growth 喂死癌症--三重芳香酸可减少肿瘤生长

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01372-9

Audrey Xavier, Ivan Dikic

引用次数: 0

The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation E3连接酶ASB3通过靶向泛素-蛋白酶体降解MAVS来下调抗病毒先天免疫能力

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01376-5

Mingyang Cheng, Yiyuan Lu, Jiarui Wang, Haixu Wang, Yu Sun, Wenhui Zhao, Junhong Wang, Chunwei Shi, Jiawei Luo, Ming Gao, Tianxin Yu, Jianzhong Wang, Jiayao Guan, Nan Wang, Wentao Yang, Yanlong Jiang, Haibin Huang, Guilian Yang, Xin Cao, Dongqin Yang, Chunfeng Wang, Yan Zeng

{"title":"The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation","authors":"Mingyang Cheng, Yiyuan Lu, Jiarui Wang, Haixu Wang, Yu Sun, Wenhui Zhao, Junhong Wang, Chunwei Shi, Jiawei Luo, Ming Gao, Tianxin Yu, Jianzhong Wang, Jiayao Guan, Nan Wang, Wentao Yang, Yanlong Jiang, Haibin Huang, Guilian Yang, Xin Cao, Dongqin Yang, Chunfeng Wang, Yan Zeng","doi":"10.1038/s41418-024-01376-5","DOIUrl":"10.1038/s41418-024-01376-5","url":null,"abstract":"E3 ubiquitin ligases are very important for regulating antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and IAV, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-β and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 presented decreased susceptibility to H9N2 and H1N1 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation of TBK1 and IRF3 and downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator that controls the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"31 12","pages":"1746-1760"},"PeriodicalIF":13.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of nucleo-cytoplasmic proteasome translocation by the aromatic amino acids or silencing Sestrin3—their sensing mediator—is tumor suppressive 通过芳香族氨基酸抑制核-细胞质蛋白酶体转运或沉默Sestrin3--它们的感应介质--具有抑瘤作用

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01370-x

Ido Livneh, Bertrand Fabre, Gilad Goldhirsh, Chen Lulu, Adar Zinger, Yael Shammai Vainer, Maya Kaduri, Aviva Dahan, Tamar Ziv, Avi Schroeder, Yinon Ben-Neriah, Yaniv Zohar, Victoria Cohen-Kaplan, Aaron Ciechanover

{"title":"Inhibition of nucleo-cytoplasmic proteasome translocation by the aromatic amino acids or silencing Sestrin3—their sensing mediator—is tumor suppressive","authors":"Ido Livneh, Bertrand Fabre, Gilad Goldhirsh, Chen Lulu, Adar Zinger, Yael Shammai Vainer, Maya Kaduri, Aviva Dahan, Tamar Ziv, Avi Schroeder, Yinon Ben-Neriah, Yaniv Zohar, Victoria Cohen-Kaplan, Aaron Ciechanover","doi":"10.1038/s41418-024-01370-x","DOIUrl":"10.1038/s41418-024-01370-x","url":null,"abstract":"The proteasome, the catalytic arm of the ubiquitin system, is regulated via its dynamic compartmentation between the nucleus and the cytoplasm, among other mechanisms. Under amino acid shortage, the proteolytic complex is translocated to the cytoplasm, where it stimulates proteolysis to supplement recycled amino acids for essential protein synthesis. This response is mediated via the mTOR pathway and the lack of the three aromatic amino acids Tyr, Trp, and Phe (YWF). mTOR activation by supplementation of the triad inhibits proteasome translocation, leading to cell death. We now show that tumoral inherent stress conditions result in translocation of the proteasome from the nucleus to the cytosol. We further show that the modulation of the signaling cascade governed by YWF is applicable also to non-starved cells by using higher concentration of the triad to achieve a surplus relative to all other amino acids. Based on these two phenomena, we found that the modulation of stress signals via the administration of YWF leads to nuclear proteasome sequestration and inhibition of growth of xenograft, spontaneous, and metastatic mouse tumor models. In correlation with the observed effect of YWF on tumors, we found – using transcriptomic and proteomic analyses – that the triad affects various cellular processes related to cell proliferation, migration, and death. In addition, Sestrin3—a mediator of YWF sensing upstream of mTOR—is essential for proteasome translocation, and therefore plays a pro-tumorigenic role, positioning it as a potential oncogene. This newly identified approach for hijacking the cellular “satiety center” carries therefore potential therapeutic implications for cancer.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"31 10","pages":"1242-1254"},"PeriodicalIF":13.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01370-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170876","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}

引用次数: 0

Correction: John F. R. Kerr (1934–2024) 更正：约翰-科尔（1934-2024）

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-12 DOI: 10.1038/s41418-024-01373-8

Margaret C. Cummings, David L. Vaux, Andreas Strasser, Ruth Kluck

引用次数: 0

Intracellular zinc protects tumours from T cell-mediated cytotoxicity 细胞内锌可保护肿瘤免受 T 细胞介导的细胞毒性影响

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-11 DOI: 10.1038/s41418-024-01369-4

Emily J. Lelliott, Jonathan Naddaf, Katherine Ganio, Jessica Michie, Shelly Wang, Lin Liu, Natasha Silke, Antonio Ahn, Kelly M. Ramsbottom, Amelia J. Brennan, Andrew J. Freeman, Shom Goel, Stephin J. Vervoort, Conor J. Kearney, Paul A. Beavis, Christopher A. McDevitt, John Silke, Jane Oliaro

{"title":"Intracellular zinc protects tumours from T cell-mediated cytotoxicity","authors":"Emily J. Lelliott, Jonathan Naddaf, Katherine Ganio, Jessica Michie, Shelly Wang, Lin Liu, Natasha Silke, Antonio Ahn, Kelly M. Ramsbottom, Amelia J. Brennan, Andrew J. Freeman, Shom Goel, Stephin J. Vervoort, Conor J. Kearney, Paul A. Beavis, Christopher A. McDevitt, John Silke, Jane Oliaro","doi":"10.1038/s41418-024-01369-4","DOIUrl":"10.1038/s41418-024-01369-4","url":null,"abstract":"Tumour immune evasion presents a significant challenge to the effectiveness of cancer immunotherapies. Recent advances in high-throughput screening techniques have uncovered that loss of antigen presentation and cytokine signalling pathways are central mechanisms by which tumours evade T cell immunity. To uncover additional vulnerabilities in tumour cells beyond the well-recognized antigen presentation pathway, we conducted a genome-wide CRISPR/Cas9 screen to identify genes that mediate resistance to chimeric-antigen receptor (CAR)-T cells, which function independently of classical antigen presentation. Our study revealed that loss of core-binding factor subunit beta (CBFβ) enhances tumour cell resistance to T cell killing, mediated through T cell-derived TNF. Mechanistically, RNA-sequencing and elemental analyses revealed that deletion of CBFβ disrupts numerous pathways including those involved in zinc homoeostasis. Moreover, we demonstrated that modulation of cellular zinc, achieved by supplementation or chelation, significantly altered tumour cell susceptibility to TNF by regulating the levels of inhibitor of apoptosis proteins. Consistent with this, treatment of tumour cells with a membrane-permeable zinc chelator had no impact on tumour cell viability alone, but significantly increased tumour cell lysis by CD8+ T cells in a TNF-dependent but perforin-independent manner. These results underscore the crucial role of intracellular zinc in regulating tumour cell susceptibility to T cell-mediated killing, revealing a novel vulnerability in tumour cells that might be exploited for the development of future cancer immunotherapeutics.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"31 12","pages":"1707-1716"},"PeriodicalIF":13.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01369-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170461","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}

引用次数: 0

Correction to: Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis 更正：两种热点突变 p53 小鼠模型在肿瘤发生过程中显示出不同的功能增益。

IF 13.7 1区生物学

Cell Death and Differentiation Pub Date : 2024-09-10 DOI: 10.1038/s41418-024-01366-7

W. Hanel, N. Marchenko, S. Xu, S. Xiaofeng Yu, W. Weng, U. Moll

引用次数: 0