Cell metabolism最新文献

The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury 综合应激反应微调了丝氨酸剥夺和组织损伤后干细胞命运的决定

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-12 DOI: 10.1016/j.cmet.2025.05.010

Jesse S.S. Novak, Lisa Polak, Sanjeethan C. Baksh, Douglas W. Barrows, Marina Schernthanner, Benjamin T. Jackson, Elizabeth A.N. Thompson, Anita Gola, M. Deniz Abdusselamoglu, Alain R. Bonny, Kevin A.U. Gonzales, Julia S. Brunner, Anna E. Bridgeman, Katie S. Stewart, Lynette Hidalgo, June Dela Cruz-Racelis, Ji-Dung Luo, Shiri Gur-Cohen, H. Amalia Pasolli, Thomas S. Carroll, Elaine Fuchs

{"title":"The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury","authors":"Jesse S.S. Novak, Lisa Polak, Sanjeethan C. Baksh, Douglas W. Barrows, Marina Schernthanner, Benjamin T. Jackson, Elizabeth A.N. Thompson, Anita Gola, M. Deniz Abdusselamoglu, Alain R. Bonny, Kevin A.U. Gonzales, Julia S. Brunner, Anna E. Bridgeman, Katie S. Stewart, Lynette Hidalgo, June Dela Cruz-Racelis, Ji-Dung Luo, Shiri Gur-Cohen, H. Amalia Pasolli, Thomas S. Carroll, Elaine Fuchs","doi":"10.1016/j.cmet.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.010","url":null,"abstract":"Epidermal stem cells produce the skin’s barrier that excludes pathogens and prevents dehydration. Hair follicle stem cells (HFSCs) are dedicated to bursts of hair regeneration, but upon injury, they can also reconstruct, and thereafter maintain, the overlying epidermis. How HFSCs balance these fate choices to restore physiologic function to damaged tissue remains poorly understood. Here, we uncover serine as an unconventional, non-essential amino acid that impacts this process. When dietary serine dips, endogenous biosynthesis in HFSCs fails to meet demands (and vice versa), slowing hair cycle entry. Serine deprivation also alters wound repair, further delaying hair regeneration while accelerating re-epithelialization kinetics. Mechanistically, we show that HFSCs sense each fitness challenge by triggering the integrated stress response, which acts as a rheostat of epidermal-HF identity. As stress levels rise, skin barrier restoration kinetics accelerate while hair growth is delayed. Our findings offer potential for dietary and pharmacological intervention to accelerate wound healing.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"589 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269254","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

Derepressing nuclear pyruvate dehydrogenase induces therapeutic cancer cell reprogramming 抑制核丙酮酸脱氢酶诱导治疗性癌细胞重编程

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-11 DOI: 10.1016/j.cmet.2025.05.009

Ting Zhao, Lingli He, Lai Ping Wong, Shenglin Mei, Jun Xia, Yanxin Xu, Jonathan G. Van Vranken, Michael Mazzola, Lei Chen, Catherine Rhee, Tiancheng Fang, Tsuyoshi Fukushima, Leanne C. Sayles, Matthew Diaz, J. Alex B. Gibbons, Raul Mostoslavsky, Steven P. Gygi, Zhixun Dou, David B. Sykes, Ruslan I. Sadreyev, David T. Scadden

{"title":"Derepressing nuclear pyruvate dehydrogenase induces therapeutic cancer cell reprogramming","authors":"Ting Zhao, Lingli He, Lai Ping Wong, Shenglin Mei, Jun Xia, Yanxin Xu, Jonathan G. Van Vranken, Michael Mazzola, Lei Chen, Catherine Rhee, Tiancheng Fang, Tsuyoshi Fukushima, Leanne C. Sayles, Matthew Diaz, J. Alex B. Gibbons, Raul Mostoslavsky, Steven P. Gygi, Zhixun Dou, David B. Sykes, Ruslan I. Sadreyev, David T. Scadden","doi":"10.1016/j.cmet.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.009","url":null,"abstract":"Metabolites are essential substrates for epigenetic modifications. Although nuclear acetyl-coenzyme A (CoA) constitutes a small fraction of the whole-cell pool, it regulates cell fate by locally providing histone acetylation substrate. Here, we report a nucleus-specific acetyl-CoA regulatory mechanism that can be modulated to achieve therapeutic cancer cell reprogramming. Combining phenotypic chemical screen, genome-wide CRISPR screen, and proteomics, we identified that the nucleus-localized pyruvate dehydrogenase complex (nPDC) is constitutively inhibited by the nuclear protein ELMSAN1 through direct interaction. Pharmacologic inhibition of the ELMSAN1-nPDC interaction derepressed nPDC activity, enhancing nuclear acetyl-CoA generation and reprogramming cancer cells to a postmitotic state with diminished cell-of-origin signatures. Reprogramming was synergistically enhanced by histone deacetylase 1/2 inhibition, resulting in inhibited tumor growth, durably suppressed tumor-initiating ability, and improved survival in multiple cancer types <em>in vivo</em>, including therapy-resistant sarcoma patient-derived xenografts and carcinoma cell line xenografts. Our findings highlight the potential of targeting ELMSAN1-nPDC as an epigenetic cancer therapy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"21 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260300","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

Genetic and physiological insights into satiation variability predict responses to obesity treatment 从遗传学和生理学角度了解饱足变异性，预测对肥胖治疗的反应

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-06 DOI: 10.1016/j.cmet.2025.05.008

Lizeth Cifuentes, Diego Anazco, Timothy O’Connor, Maria Daniela Hurtado, Wissam Ghusn, Alejandro Campos, Sima Fansa, Alison McRae, Sunil Madhusudhan, Elle Kolkin, Michael Ryks, William S. Harmsen, Serban Ciotlos, Barham K. Abu Dayyeh, Donald D. Hensrud, Michael Camilleri, Andres Acosta

{"title":"Genetic and physiological insights into satiation variability predict responses to obesity treatment","authors":"Lizeth Cifuentes, Diego Anazco, Timothy O’Connor, Maria Daniela Hurtado, Wissam Ghusn, Alejandro Campos, Sima Fansa, Alison McRae, Sunil Madhusudhan, Elle Kolkin, Michael Ryks, William S. Harmsen, Serban Ciotlos, Barham K. Abu Dayyeh, Donald D. Hensrud, Michael Camilleri, Andres Acosta","doi":"10.1016/j.cmet.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.008","url":null,"abstract":"Satiation, the process that regulates meal size and termination, varies widely among adults with obesity. To better understand and leverage this variability, we assessed calories to satiation (CTS) through an <em>ad libitum</em> meal, combined with physiological and behavioral evaluations, including calorimetry, imaging, blood sampling, and gastric emptying tests. Although factors like baseline characteristics, body composition, and hormone levels partially explain CTS variability, they leave substantial variability unaccounted for. To address this gap, we developed a machine-learning-assisted genetic risk score (CTS<sub>GRS</sub>) to predict high CTS. In a randomized clinical trial, participants with high CTS or CTS<sub>GRS</sub> achieved greater weight loss with phentermine-topiramate over 52 weeks, whereas those with low CTS or CTS<sub>GRS</sub> responded better to liraglutide at 16 weeks in a separate trial. These findings highlight the potential of combining satiation measurements with genetic modeling to predict treatment outcomes and inform personalized strategies for obesity management.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"60 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228676","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

Metabolic switches in cell death regulation 细胞死亡调控中的代谢开关

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.04.017

Lorenzo Galluzzi

引用次数: 0

Cell Metabolism 20th anniversary Voices: Part 3 of 3 细胞代谢20周年纪念声音：三集之三

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.05.006

Matthew Potthoff, Rana K. Gupta, Changhan Lee, Jonathan Z. Long, Jonathan R. Brestoff, Katrien de Bock

引用次数: 0

Testing the carbohydrate-insulin model: Some aspects are consistent, but overall the data do not support the model 测试碳水化合物-胰岛素模型：某些方面是一致的，但总体数据不支持模型

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.04.011

John R. Speakman, Ying Liu

引用次数: 0

Time to exercise! Boosting exercise performance via AMPK signaling 是时候锻炼了！通过AMPK信号传导提高运动表现

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.05.003

Tinh-Hai Collet, Charna Dibner

引用次数: 0

GLP-1RAs for peripheral artery disease: A remarkable STRIDE in the right direction GLP-1RAs治疗外周动脉疾病：朝着正确方向迈出的一大步

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.05.001

Subodh Verma, David A. Hess

引用次数: 0

Testing the carbohydrate-insulin model: The data are supportive! 测试碳水化合物-胰岛素模型：数据是支持的！

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.04.010

David S. Ludwig, Jennie C. Brand-Miller, Cara B. Ebbeling, Mark I. Friedman, Nicholas G. Norwitz, Adrian Soto-Mota

{"title":"Testing the carbohydrate-insulin model: The data are supportive!","authors":"David S. Ludwig, Jennie C. Brand-Miller, Cara B. Ebbeling, Mark I. Friedman, Nicholas G. Norwitz, Adrian Soto-Mota","doi":"10.1016/j.cmet.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.010","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Mean body weight continues to rise worldwide despite intensive prevention and treatment focused on energy restriction, leading to formulation of new models of obesity pathogenesis. In the carbohydrate-insulin model (CIM),<sup>1</sup> a diet high in glycemic load (GL) (the multiplicative product of glycemic index [GI] and carbohydrate amount) initiates a sequence of hormonal responses that shift substrate partitioning<sup>2</sup> toward energy storage and away from oxidation in lean tissues. Thus, the CIM provides an</section></section><section><section><h2>Acknowledgments</h2>This work was done without financial sponsorship.</section></section><section><section><h2>Declaration of interests</h2>J.B.M. is a co-author of books based on the glycemic index of foods, oversees a glycemic index testing service at the University of Sydney, and is a consultant for the China National Research Institute of Food and Fermentation Industries, the Novo Foundation, and Zoe Global. She was President of the Glycemic Index Foundation from 2002 to 2024. D.S.L received royalties for books on obesity and nutrition that recommend a reduced-glycemic load diet. N.G.N. received royalties for a ketogenic diet</section></section>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"4 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144202290","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

CROSsing the Rubicon: Brainstem peroxide levels drive sleep-wake dynamics 跨越卢比孔河：脑干过氧化氢水平驱动睡眠-觉醒动力学

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.05.005

Nicole M. Gilette, Jonathan O. Lipton

引用次数: 0