Cell metabolism最新文献_第2页

Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic β cells. 细胞膜 pH 值是连接环境线索与胰岛β细胞胰岛素加工和分泌的直接纽带。

Cell metabolism Pub Date : 2024-06-04 Epub Date: 2024-03-20 DOI: 10.1016/j.cmet.2024.02.012

Yujiang Fang, Hexi Feng, Bowen Zhang, Shuwei Zhang, Yanjie Zhou, Pengcheng Hao, Zhongshu Zhou, Shanshan Zhou, Nan Li, Yi Hui, Lin Ma, Jie Xiong, Jinjin Wu, Ling Liu, Xiaoqing Zhang

{"title":"Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic β cells.","authors":"Yujiang Fang, Hexi Feng, Bowen Zhang, Shuwei Zhang, Yanjie Zhou, Pengcheng Hao, Zhongshu Zhou, Shanshan Zhou, Nan Li, Yi Hui, Lin Ma, Jie Xiong, Jinjin Wu, Ling Liu, Xiaoqing Zhang","doi":"10.1016/j.cmet.2024.02.012","DOIUrl":"10.1016/j.cmet.2024.02.012","url":null,"abstract":"Pancreatic β cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as β cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in β cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in β cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in β cells.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1237-1251.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic, epigenomic, and spatial metabolomic cell profiling redefines regional human kidney anatomy. 转录组学、表观基因组学和空间代谢组学细胞剖析重新定义了区域人类肾脏解剖学。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-20 DOI: 10.1016/j.cmet.2024.02.015

Haikuo Li, Dian Li, Nicolas Ledru, Qiao Xuanyuan, Haojia Wu, Amish Asthana, Lori N Byers, Stefan G Tullius, Giuseppe Orlando, Sushrut S Waikar, Benjamin D Humphreys

{"title":"Transcriptomic, epigenomic, and spatial metabolomic cell profiling redefines regional human kidney anatomy.","authors":"Haikuo Li, Dian Li, Nicolas Ledru, Qiao Xuanyuan, Haojia Wu, Amish Asthana, Lori N Byers, Stefan G Tullius, Giuseppe Orlando, Sushrut S Waikar, Benjamin D Humphreys","doi":"10.1016/j.cmet.2024.02.015","DOIUrl":"10.1016/j.cmet.2024.02.015","url":null,"abstract":"A large-scale multimodal atlas that includes major kidney regions is lacking. Here, we employed simultaneous high-throughput single-cell ATAC/RNA sequencing (SHARE-seq) and spatially resolved metabolomics to profile 54 human samples from distinct kidney anatomical regions. We generated transcriptomes of 446,267 cells and chromatin accessibility profiles of 401,875 cells and developed a package to analyze 408,218 spatially resolved metabolomes. We find that the same cell type, including thin limb, thick ascending limb loop of Henle and principal cells, display distinct transcriptomic, chromatin accessibility, and metabolomic signatures, depending on anatomic location. Surveying metabolism-associated gene profiles revealed non-overlapping metabolic signatures between nephron segments and dysregulated lipid metabolism in diseased proximal tubule (PT) cells. Integrating multimodal omics with clinical data identified PLEKHA1 as a disease marker, and its in vitro knockdown increased gene expression in PT differentiation, suggesting possible pathogenic roles. This study highlights previously underrepresented cellular heterogeneity underlying the human kidney anatomy.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1105-1125.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of pregnancy, its progression, and its cessation on human (maternal) biological aging. 妊娠、妊娠进展和妊娠停止对人类（母体）生物衰老的影响。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-22 DOI: 10.1016/j.cmet.2024.02.016

Hung Pham, Tara Thompson-Felix, Darina Czamara, Jerod M Rasmussen, Adam Lombroso, Sonja Entringer, Elisabeth B Binder, Pathik D Wadhwa, Claudia Buss, Kieran J O'Donnell

引用次数: 0

Physiologic disruption and metabolic reprogramming in infection and sepsis. 感染和败血症中的生理紊乱和新陈代谢重编程。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-20 DOI: 10.1016/j.cmet.2024.02.013

Katharina Willmann, Luis F Moita

引用次数: 0

Aging-induced tRNA^Glu-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization. 老化诱导的 tRNAGlu 衍生片段通过靶向线粒体翻译依赖性嵴组织来损害谷氨酸的生物合成。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-07 DOI: 10.1016/j.cmet.2024.02.011

Dingfeng Li, Xinyi Gao, Xiaolin Ma, Ming Wang, Chuandong Cheng, Tian Xue, Feng Gao, Yong Shen, Juan Zhang, Qiang Liu

{"title":"Aging-induced tRNAGlu-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization.","authors":"Dingfeng Li, Xinyi Gao, Xiaolin Ma, Ming Wang, Chuandong Cheng, Tian Xue, Feng Gao, Yong Shen, Juan Zhang, Qiang Liu","doi":"10.1016/j.cmet.2024.02.011","DOIUrl":"10.1016/j.cmet.2024.02.011","url":null,"abstract":"Mitochondrial cristae, infoldings of the mitochondrial inner membrane, undergo aberrant changes in their architecture with age. However, the underlying molecular mechanisms and their contribution to brain aging are largely elusive. Here, we observe an age-dependent accumulation of Glu-5'tsRNA-CTC, a transfer-RNA-derived small RNA (tsRNA), derived from nuclear-encoded tRNAGlu in the mitochondria of glutaminergic neurons. Mitochondrial Glu-5'tsRNA-CTC disrupts the binding of mt-tRNALeu and leucyl-tRNA synthetase2 (LaRs2), impairing mt-tRNALeu aminoacylation and mitochondria-encoded protein translation. Mitochondrial translation defects disrupt cristae organization, leading to damaged glutaminase (GLS)-dependent glutamate formation and reduced synaptosomal glutamate levels. Moreover, reduction of Glu-5'tsRNA-CTC protects aged brains from age-related defects in mitochondrial cristae organization, glutamate metabolism, synaptic structures, and memory. Thus, beyond illustrating a physiological role for normal mitochondrial cristae ultrastructure in maintaining glutamate levels, our study defines a pathological role for tsRNAs in brain aging and age-related memory decline.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1059-1075.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity. 转酮醇酶通过限制肌苷诱导的线粒体活性来促进 MAFLD。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-27 DOI: 10.1016/j.cmet.2024.03.003

Lingfeng Tong, Zhangbing Chen, Yangyang Li, Xinxia Wang, Changjie Yang, Yakui Li, Yemin Zhu, Ying Lu, Qi Liu, Nannan Xu, Sijia Shao, Lifang Wu, Ping Zhang, Guangyu Wu, Xiaoyu Wu, Xiaosong Chen, Junwei Fang, Renbing Jia, Tianle Xu, Bin Li, Liang Zheng, Junling Liu, Xuemei Tong

{"title":"Transketolase promotes MAFLD by limiting inosine-induced mitochondrial activity.","authors":"Lingfeng Tong, Zhangbing Chen, Yangyang Li, Xinxia Wang, Changjie Yang, Yakui Li, Yemin Zhu, Ying Lu, Qi Liu, Nannan Xu, Sijia Shao, Lifang Wu, Ping Zhang, Guangyu Wu, Xiaoyu Wu, Xiaosong Chen, Junwei Fang, Renbing Jia, Tianle Xu, Bin Li, Liang Zheng, Junling Liu, Xuemei Tong","doi":"10.1016/j.cmet.2024.03.003","DOIUrl":"10.1016/j.cmet.2024.03.003","url":null,"abstract":"Metabolic dysfunction-associated fatty liver disease (MAFLD) has a global prevalence of about 25% and no approved therapy. Using metabolomic and proteomic analyses, we identified high expression of hepatic transketolase (TKT), a metabolic enzyme of the pentose phosphate pathway, in human and mouse MAFLD. Hyperinsulinemia promoted TKT expression through the insulin receptor-CCAAT/enhancer-binding protein alpha axis. Utilizing liver-specific TKT overexpression and knockout mouse models, we demonstrated that TKT was sufficient and required for MAFLD progression. Further metabolic flux analysis revealed that Tkt deletion increased hepatic inosine levels to activate the protein kinase A-cAMP response element binding protein cascade, promote phosphatidylcholine synthesis, and improve mitochondrial function. Moreover, insulin induced hepatic TKT to limit inosine-dependent mitochondrial activity. Importantly, N-acetylgalactosamine (GalNAc)-siRNA conjugates targeting hepatic TKT showed promising therapeutic effects on mouse MAFLD. Our study uncovers how hyperinsulinemia regulates TKT-orchestrated inosine metabolism and mitochondrial function and provides a novel therapeutic strategy for MAFLD prevention and treatment.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1013-1029.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fndc5 is translated from an upstream ATG start codon and cleaved to produce irisin myokine precursor protein in humans and mice. 在人和小鼠体内，Fndc5 从上游 ATG 起始密码子翻译并裂解产生鸢尾素肌动蛋白前体蛋白。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-11 DOI: 10.1016/j.cmet.2024.02.008

Nathan H Witmer, Connor R Linzer, Ryan L Boudreau

引用次数: 0

Acetyl-CoA carboxylase obstructs CD8⁺ T cell lipid utilization in the tumor microenvironment. 乙酰-CoA羧化酶阻碍 CD8+ T 细胞在肿瘤微环境中利用脂质

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-14 DOI: 10.1016/j.cmet.2024.02.009

Elizabeth G Hunt, Katie E Hurst, Brian P Riesenberg, Andrew S Kennedy, Evelyn J Gandy, Alex M Andrews, Coral Del Mar Alicea Pauneto, Lauren E Ball, Emily D Wallace, Peng Gao, Jeremy Meier, John J Serody, Michael F Coleman, Jessica E Thaxton

{"title":"Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment.","authors":"Elizabeth G Hunt, Katie E Hurst, Brian P Riesenberg, Andrew S Kennedy, Evelyn J Gandy, Alex M Andrews, Coral Del Mar Alicea Pauneto, Lauren E Ball, Emily D Wallace, Peng Gao, Jeremy Meier, John J Serody, Michael F Coleman, Jessica E Thaxton","doi":"10.1016/j.cmet.2024.02.009","DOIUrl":"10.1016/j.cmet.2024.02.009","url":null,"abstract":"The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors. We reveal that the solid TME imposes perpetual acetyl-coenzyme A (CoA) carboxylase (ACC) activity, invoking lipid biogenesis and storage in TILs that opposes FAO. Using metabolic, lipidomic, and confocal imaging strategies, we find that restricting ACC rewires T cell metabolism, enabling energy maintenance in TME stress. Limiting ACC activity potentiates a gene and phenotypic program indicative of T cell longevity, engendering T cells with increased survival and polyfunctionality, which sustains cancer control.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"969-983.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8⁺T cells. 肿瘤分泌的 FGF21 可通过重新连接 CD8+T 细胞的胆固醇代谢来发挥免疫抑制作用。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-26 DOI: 10.1016/j.cmet.2024.03.013

Cegui Hu, Wen Qiao, Xiang Li, Zhi-Kun Ning, Jiang Liu, Sumiya Dalangood, Hanjun Li, Xiang Yu, Zhen Zong, Zhenke Wen, Jun Gui

引用次数: 0

Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability. 肝脏丙二酰-CoA 的合成通过抑制脂肪氧化、丙酮酸羧化和氨基酸供应来抑制葡萄糖生成。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-05 DOI: 10.1016/j.cmet.2024.02.004

Stanislaw Deja, Justin A Fletcher, Chai-Wan Kim, Blanka Kucejova, Xiaorong Fu, Monika Mizerska, Morgan Villegas, Natalia Pudelko-Malik, Nicholas Browder, Melissa Inigo-Vollmer, Cameron J Menezes, Prashant Mishra, Eric D Berglund, Jeffrey D Browning, John P Thyfault, Jamey D Young, Jay D Horton, Shawn C Burgess

{"title":"Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability.","authors":"Stanislaw Deja, Justin A Fletcher, Chai-Wan Kim, Blanka Kucejova, Xiaorong Fu, Monika Mizerska, Morgan Villegas, Natalia Pudelko-Malik, Nicholas Browder, Melissa Inigo-Vollmer, Cameron J Menezes, Prashant Mishra, Eric D Berglund, Jeffrey D Browning, John P Thyfault, Jamey D Young, Jay D Horton, Shawn C Burgess","doi":"10.1016/j.cmet.2024.02.004","DOIUrl":"10.1016/j.cmet.2024.02.004","url":null,"abstract":"Acetyl-CoA carboxylase (ACC) promotes prandial liver metabolism by producing malonyl-CoA, a substrate for de novo lipogenesis and an inhibitor of CPT-1-mediated fat oxidation. We report that inhibition of ACC also produces unexpected secondary effects on metabolism. Liver-specific double ACC1/2 knockout (LDKO) or pharmacologic inhibition of ACC increased anaplerosis, tricarboxylic acid (TCA) cycle intermediates, and gluconeogenesis by activating hepatic CPT-1 and pyruvate carboxylase flux in the fed state. Fasting should have marginalized the role of ACC, but LDKO mice maintained elevated TCA cycle intermediates and preserved glycemia during fasting. These effects were accompanied by a compensatory induction of proteolysis and increased amino acid supply for gluconeogenesis, which was offset by increased protein synthesis during feeding. Such adaptations may be related to Nrf2 activity, which was induced by ACC inhibition and correlated with fasting amino acids. The findings reveal unexpected roles for malonyl-CoA synthesis in liver and provide insight into the broader effects of pharmacologic ACC inhibition.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"1088-1104.e12"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0