Cell metabolismPub Date : 2024-07-09DOI: 10.1016/j.cmet.2024.06.010
Lynn Bonetti, Veronika Horkova, Melanie Grusdat, Joseph Longworth, Luana Guerra, Henry Kurniawan, Davide G. Franchina, Leticia Soriano-Baguet, Carole Binsfeld, Charlène Verschueren, Sabine Spath, Anouk Ewen, Eric Koncina, Jean-Jacques Gérardy, Takumi Kobayashi, Catherine Dostert, Sophie Farinelle, Janika Härm, Yu-Tong Fan, Ying Chen, Dirk Brenner
{"title":"A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation","authors":"Lynn Bonetti, Veronika Horkova, Melanie Grusdat, Joseph Longworth, Luana Guerra, Henry Kurniawan, Davide G. Franchina, Leticia Soriano-Baguet, Carole Binsfeld, Charlène Verschueren, Sabine Spath, Anouk Ewen, Eric Koncina, Jean-Jacques Gérardy, Takumi Kobayashi, Catherine Dostert, Sophie Farinelle, Janika Härm, Yu-Tong Fan, Ying Chen, Dirk Brenner","doi":"10.1016/j.cmet.2024.06.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.010","url":null,"abstract":"<p>The intestinal tract generates significant reactive oxygen species (ROS), but the role of T cell antioxidant mechanisms in maintaining intestinal homeostasis is poorly understood. We used T cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (<em>Gclc</em>), which impaired glutathione (GSH) production, crucially reducing IL-22 production by Th17 cells in the lamina propria, which is critical for gut protection. Under steady-state conditions, <em>Gclc</em> deficiency did not alter cytokine secretion; however, <em>C. rodentium</em> infection induced increased ROS and disrupted mitochondrial function and TFAM-driven mitochondrial gene expression, resulting in decreased cellular ATP. These changes impaired the PI3K/AKT/mTOR pathway, reducing phosphorylation of 4E-BP1 and consequently limiting IL-22 translation. The resultant low IL-22 levels led to poor bacterial clearance, severe intestinal damage, and high mortality. Our findings highlight a previously unrecognized, essential role of Th17 cell-intrinsic GSH in promoting mitochondrial function and cellular signaling for IL-22 protein synthesis, which is critical for intestinal integrity and defense against gastrointestinal infections.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"35 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561667","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}
Cell metabolismPub Date : 2024-07-03DOI: 10.1016/j.cmet.2024.06.007
Travis Nemkov, Daniel Stephenson, Eric J. Earley, Gregory R. Keele, Ariel Hay, Alicia Key, Zachary B. Haiman, Christopher Erickson, Monika Dzieciatkowska, Julie A. Reisz, Amy Moore, Mars Stone, Xutao Deng, Steven Kleinman, Steven L. Spitalnik, Eldad A. Hod, Krystalyn E. Hudson, Kirk C. Hansen, Bernhard O. Palsson, Gary A. Churchill, Angelo D’Alessandro
{"title":"Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes","authors":"Travis Nemkov, Daniel Stephenson, Eric J. Earley, Gregory R. Keele, Ariel Hay, Alicia Key, Zachary B. Haiman, Christopher Erickson, Monika Dzieciatkowska, Julie A. Reisz, Amy Moore, Mars Stone, Xutao Deng, Steven Kleinman, Steven L. Spitalnik, Eldad A. Hod, Krystalyn E. Hudson, Kirk C. Hansen, Bernhard O. Palsson, Gary A. Churchill, Angelo D’Alessandro","doi":"10.1016/j.cmet.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.007","url":null,"abstract":"<p>Mature red blood cells (RBCs) lack mitochondria and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging <em>in vivo</em> or storage in blood banks. Here, we leveraged 13,029 volunteers from the Recipient Epidemiology and Donor Evaluation Study to identify associations between end-of-storage levels of glycolytic metabolites and donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding phosphofructokinase 1, platelet (detected in mature RBCs); hexokinase 1 (HK1); and ADP-ribosyl cyclase 1 and 2 (CD38/BST1). Gene-metabolite associations were validated in fresh and stored RBCs from 525 Diversity Outbred mice and via multi-omics characterization of 1,929 samples from 643 human RBC units during storage. ATP and hypoxanthine (HYPX) levels—and the genetic traits linked to them—were associated with hemolysis <em>in vitro</em> and <em>in vivo</em>, both in healthy autologous transfusion recipients and in 5,816 critically ill patients receiving heterologous transfusions, suggesting their potential as markers to improve transfusion outcomes.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"93 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496022","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}
Cell metabolismPub Date : 2024-07-02DOI: 10.1016/j.cmet.2024.06.004
Min Seo Kim, Injeong Shim, Akl C. Fahed, Ron Do, Woong-Yang Park, Pradeep Natarajan, Amit V. Khera, Hong-Hee Won
{"title":"Association of genetic risk, lifestyle, and their interaction with obesity and obesity-related morbidities","authors":"Min Seo Kim, Injeong Shim, Akl C. Fahed, Ron Do, Woong-Yang Park, Pradeep Natarajan, Amit V. Khera, Hong-Hee Won","doi":"10.1016/j.cmet.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.004","url":null,"abstract":"<p>The extent to which modifiable lifestyle factors offset the determined genetic risk of obesity and obesity-related morbidities remains unknown. We explored how the interaction between genetic and lifestyle factors influences the risk of obesity and obesity-related morbidities. The polygenic score for body mass index was calculated to quantify inherited susceptibility to obesity in 338,645 UK Biobank European participants, and a composite lifestyle score was derived from five obesogenic factors (physical activity, diet, sedentary behavior, alcohol consumption, and sleep duration). We observed significant interaction between high genetic risk and poor lifestyles (<em>p</em><sub>interaction</sub> < 0.001). Absolute differences in obesity risk between those who adhere to healthy lifestyles and those who do not had gradually expanded with an increase in polygenic score. Despite a high genetic risk for obesity, individuals can prevent obesity-related morbidities by adhering to a healthy lifestyle and maintaining a normal body weight. Healthy lifestyles should be promoted irrespective of genetic background.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"44 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489802","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}
Cell metabolismPub Date : 2024-07-02DOI: 10.1016/j.cmet.2024.06.002
Kevin A. Janssen, Angela Song
{"title":"From whence it came: Mitochondrial mRNA leaves, a protein returns","authors":"Kevin A. Janssen, Angela Song","doi":"10.1016/j.cmet.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.002","url":null,"abstract":"<p>Small peptides have previously been reported to be encoded in mitochondrial rRNA and translated by cytosolic ribosomes. In this issue of <em>Cell Metabolism</em>, Hu et al. use mass spectrometry to identify a cytosolically translated protein, encoded instead in mitochondrial mRNA, that is surprisingly targeted back into the mitochondrial matrix.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"2015 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489682","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}
Cell metabolismPub Date : 2024-07-02DOI: 10.1016/j.cmet.2024.06.003
Marc R. Bornstein, Rong Tian, Zoltan Arany
{"title":"Human cardiac metabolism","authors":"Marc R. Bornstein, Rong Tian, Zoltan Arany","doi":"10.1016/j.cmet.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.003","url":null,"abstract":"<p>The heart is the most metabolically active organ in the human body, and cardiac metabolism has been studied for decades. However, the bulk of studies have focused on animal models. The objective of this review is to summarize specifically what is known about cardiac metabolism in humans. Techniques available to study human cardiac metabolism are first discussed, followed by a review of human cardiac metabolism in health and in heart failure. Mechanistic insights, where available, are reviewed, and the evidence for the contribution of metabolic insufficiency to heart failure, as well as past and current attempts at metabolism-based therapies, is also discussed.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"24 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489815","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}
Cell metabolismPub Date : 2024-07-02DOI: 10.1016/j.cmet.2024.06.001
Jelena Kolic, WenQing Grace Sun, Haoning Howard Cen, Jessica D. Ewald, Jason C. Rogalski, Shugo Sasaki, Han Sun, Varsha Rajesh, Yi Han Xia, Renata Moravcova, Søs Skovsø, Aliya F. Spigelman, Jocelyn E. Manning Fox, James Lyon, Leanne Beet, Jianguo Xia, Francis C. Lynn, Anna L. Gloyn, Leonard J. Foster, Patrick E. MacDonald, James D. Johnson
{"title":"Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease","authors":"Jelena Kolic, WenQing Grace Sun, Haoning Howard Cen, Jessica D. Ewald, Jason C. Rogalski, Shugo Sasaki, Han Sun, Varsha Rajesh, Yi Han Xia, Renata Moravcova, Søs Skovsø, Aliya F. Spigelman, Jocelyn E. Manning Fox, James Lyon, Leanne Beet, Jianguo Xia, Francis C. Lynn, Anna L. Gloyn, Leonard J. Foster, Patrick E. MacDonald, James D. Johnson","doi":"10.1016/j.cmet.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.001","url":null,"abstract":"<p>Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors’ islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors’ islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein—potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"19 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496028","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}
Cell metabolismPub Date : 2024-07-02DOI: 10.1016/j.cmet.2024.06.011
Sarah J. Pickett, Robert W. Taylor, Robert McFarland
{"title":"Fit for purpose: Selecting the best mitochondrial DNA for the job","authors":"Sarah J. Pickett, Robert W. Taylor, Robert McFarland","doi":"10.1016/j.cmet.2024.06.011","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.011","url":null,"abstract":"<p>The factors determining levels of pathogenic mitochondrial DNA in cells and tissues are critical to disease pathology but remain poorly understood and contentious. In <em>Nature</em>, Kotrys et al. published a single-cell-based analysis casting fresh light on this thorny problem and introduced a powerful new investigative tool.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"7 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489658","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}
Cell metabolismPub Date : 2024-07-02DOI: 10.1016/j.cmet.2024.05.012
Zhengqing Yu, Yong Zhou, Kehang Mao, Bo Pang, Kai Wang, Tang Jin, Haonan Zheng, Haotian Zhai, Yiyang Wang, Xiaohan Xu, Hongxiao Liu, Yi Wang, Jing-Dong J. Han
{"title":"Thermal facial image analyses reveal quantitative hallmarks of aging and metabolic diseases","authors":"Zhengqing Yu, Yong Zhou, Kehang Mao, Bo Pang, Kai Wang, Tang Jin, Haonan Zheng, Haotian Zhai, Yiyang Wang, Xiaohan Xu, Hongxiao Liu, Yi Wang, Jing-Dong J. Han","doi":"10.1016/j.cmet.2024.05.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.05.012","url":null,"abstract":"<p>Although human core body temperature is known to decrease with age, the age dependency of facial temperature and its potential to indicate aging rate or aging-related diseases remains uncertain. Here, we collected thermal facial images of 2,811 Han Chinese individuals 20–90 years old, developed the ThermoFace method to automatically process and analyze images, and then generated thermal age and disease prediction models. The ThermoFace deep learning model for thermal facial age has a mean absolute deviation of about 5 years in cross-validation and 5.18 years in an independent cohort. The difference between predicted and chronological age is highly associated with metabolic parameters, sleep time, and gene expression pathways like DNA repair, lipolysis, and ATPase in the blood transcriptome, and it is modifiable by exercise. Consistently, ThermoFace disease predictors forecast metabolic diseases like fatty liver with high accuracy (AUC > 0.80), with predicted disease probability correlated with metabolic parameters.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"63 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489763","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}
Cell metabolismPub Date : 2024-07-02DOI: 10.1016/j.cmet.2024.06.006
Ralph Patrick, Marina Naval-Sanchez, Nikita Deshpande, Yifei Huang, Jingyu Zhang, Xiaoli Chen, Ying Yang, Kanupriya Tiwari, Mohammadhossein Esmaeili, Minh Tran, Amin R. Mohamed, Binxu Wang, Di Xia, Jun Ma, Jacqueline Bayliss, Kahlia Wong, Michael L. Hun, Xuan Sun, Benjamin Cao, Denny L. Cottle, Christian M. Nefzger
{"title":"The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening","authors":"Ralph Patrick, Marina Naval-Sanchez, Nikita Deshpande, Yifei Huang, Jingyu Zhang, Xiaoli Chen, Ying Yang, Kanupriya Tiwari, Mohammadhossein Esmaeili, Minh Tran, Amin R. Mohamed, Binxu Wang, Di Xia, Jun Ma, Jacqueline Bayliss, Kahlia Wong, Michael L. Hun, Xuan Sun, Benjamin Cao, Denny L. Cottle, Christian M. Nefzger","doi":"10.1016/j.cmet.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.006","url":null,"abstract":"<p>A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate <em>cis</em>-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"34 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489814","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}
Cell metabolismPub Date : 2024-06-29DOI: 10.1016/j.cmet.2024.06.012
Ajit Regmi, Eitaro Aihara, Michael E. Christe, Gabor Varga, Thomas P. Beyer, Xiaoping Ruan, Emily Beebe, Libbey S. O’Farrell, Melissa A. Bellinger, Aaron K. Austin, Yanzhu Lin, Haitao Hu, Debra L. Konkol, Samantha Wojnicki, Adrienne K. Holland, Jessica L. Friedrich, Robert A. Brown, Amanda S. Estelle, Hannah S. Badger, Gabriel S. Gaidosh, William Roell
{"title":"Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor","authors":"Ajit Regmi, Eitaro Aihara, Michael E. Christe, Gabor Varga, Thomas P. Beyer, Xiaoping Ruan, Emily Beebe, Libbey S. O’Farrell, Melissa A. Bellinger, Aaron K. Austin, Yanzhu Lin, Haitao Hu, Debra L. Konkol, Samantha Wojnicki, Adrienne K. Holland, Jessica L. Friedrich, Robert A. Brown, Amanda S. Estelle, Hannah S. Badger, Gabriel S. Gaidosh, William Roell","doi":"10.1016/j.cmet.2024.06.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2024.06.012","url":null,"abstract":"No Abstract","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"54 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141463539","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}
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