Cell metabolism最新文献_第8页

Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma 糖代谢重编程诱导的 XRCC1 乳化作用使表达 ALDH1A3 的胶质母细胞瘤产生抗药性

IF 29 1区生物学

Cell metabolism Pub Date : 2024-08-06 DOI: 10.1016/j.cmet.2024.07.011

{"title":"Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma","authors":"","doi":"10.1016/j.cmet.2024.07.011","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.07.011","url":null,"abstract":"Patients with high ALDH1A3-expressing glioblastoma (ALDH1A3hi GBM) show limited benefit from postoperative chemoradiotherapy. Understanding the mechanisms underlying such resistance in these patients is crucial for the development of new treatments. Here, we show that the interaction between ALDH1A3 and PKM2 enhances the latter’s tetramerization and promotes lactate accumulation in glioblastoma stem cells (GSCs). By scanning the lactylated proteome in lactate-accumulating GSCs, we show that XRCC1 undergoes lactylation at lysine 247 (K247). Lactylated XRCC1 shows a stronger affinity for importin α, allowing for greater nuclear transposition of XRCC1 and enhanced DNA repair. Through high-throughput screening of a small-molecule library, we show that D34-919 potently disrupts the ALDH1A3-PKM2 interaction, preventing the ALDH1A3-mediated enhancement of PKM2 tetramerization. In vitro and in vivo treatment with D34-919 enhanced chemoradiotherapy-induced apoptosis of GBM cells. Together, our findings show that ALDH1A3-mediated PKM2 tetramerization is a potential therapeutic target to improve the response to chemoradiotherapy in ALDH1A3hi GBM.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"2 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895782","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

Lactylation: Linking the Warburg effect to DNA damage repair 乳化作用：将沃伯格效应与 DNA 损伤修复联系起来

IF 29 1区生物学

Cell metabolism Pub Date : 2024-08-06 DOI: 10.1016/j.cmet.2024.06.015

引用次数: 0

Zinc transporter 1 functions in copper uptake and cuproptosis 锌转运体 1 在铜吸收和铜中毒中的功能

IF 29 1区生物学

Cell metabolism Pub Date : 2024-08-06 DOI: 10.1016/j.cmet.2024.07.009

引用次数: 0

Hepatic BMAL1 and HIF1α regulate a time-dependent hypoxic response and prevent hepatopulmonary-like syndrome 肝脏 BMAL1 和 HIF1α 可调节时间依赖性缺氧反应并预防肝肺样综合征

IF 29 1区生物学

Cell metabolism Pub Date : 2024-08-05 DOI: 10.1016/j.cmet.2024.07.003

{"title":"Hepatic BMAL1 and HIF1α regulate a time-dependent hypoxic response and prevent hepatopulmonary-like syndrome","authors":"","doi":"10.1016/j.cmet.2024.07.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.07.003","url":null,"abstract":"The transcriptional response to hypoxia is temporally regulated, yet the molecular underpinnings and physiological implications are unknown. We examined the roles of hepatic Bmal1 and Hif1α in the circadian response to hypoxia in mice. We found that the majority of the transcriptional response to hypoxia is dependent on either Bmal1 or Hif1α, through shared and distinct roles that are daytime determined. We further show that hypoxia-inducible factor (HIF)1α accumulation upon hypoxia is temporally regulated and Bmal1 dependent. Unexpectedly, mice lacking both hepatic Bmal1 and Hif1α are hypoxemic and exhibit increased mortality upon hypoxic exposure in a daytime-dependent manner. These mice display mild liver dysfunction with pulmonary vasodilation likely due to extracellular signaling regulated kinase (ERK) activation, endothelial nitric oxide synthase, and nitric oxide accumulation in lungs, suggestive of hepatopulmonary syndrome. Our findings indicate that hepatic BMAL1 and HIF1α are key time-dependent regulators of the hypoxic response and can provide molecular insights into the pathophysiology of hepatopulmonary syndrome.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"29 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892160","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

Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes 单核转录组学识别出不同类别的 UCP1 和无效周期脂肪细胞

IF 29 1区生物学

Cell metabolism Pub Date : 2024-07-30 DOI: 10.1016/j.cmet.2024.07.005

引用次数: 0

Development of a functional beige fat cell line uncovers independent subclasses of cells expressing UCP1 and the futile creatine cycle 功能性米色脂肪细胞系的开发揭示了表达 UCP1 和无效肌酸循环的独立细胞亚类

IF 29 1区生物学

Cell metabolism Pub Date : 2024-07-30 DOI: 10.1016/j.cmet.2024.07.002

引用次数: 0

A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH 一种微生物代谢物抑制 HIF-2α 神经酰胺通路，从而介导限时进食对 MASH 的有益影响

IF 29 1区生物学

Cell metabolism Pub Date : 2024-07-29 DOI: 10.1016/j.cmet.2024.07.004