Jiaxing Wang , Qiangzhou Wang , Xinrui Li , Qingqing Cai , Yulin Bi , Chenyang Xu , Hao Bai , Lihong Gu , Guobin Chang , Shihao Chen
{"title":"TRIM在代谢调节中的新作用","authors":"Jiaxing Wang , Qiangzhou Wang , Xinrui Li , Qingqing Cai , Yulin Bi , Chenyang Xu , Hao Bai , Lihong Gu , Guobin Chang , Shihao Chen","doi":"10.1016/j.metabol.2025.156394","DOIUrl":null,"url":null,"abstract":"<div><div>Recent findings have broadened our understanding of the tripartite motif (TRIM) protein family, positioning these proteins as pivotal regulators of cellular metabolism and cell fate. Primarily functioning as versatile E3 ubiquitin ligases, TRIM proteins orchestrate key metabolic pathways—including glucose, lipid, and amino acid metabolism—through both ubiquitination-dependent and -independent mechanisms such as oligomerization and epigenetic modification. For example, TRIM38, TRIM11, and TRIM24 have been reported to modulate glycolytic flux and insulin signaling by targeting key glucose transporters and glycolytic enzymes, with effects on cancer metabolism and insulin responses in model systems. Similarly, TRIM21 and TRIM56 have been implicated in fatty acid synthesis, oxidation, and cholesterol balance, with potential relevance to fatty-liver conditions and atherosclerosis. Moreover, TRIM-mediated regulation of amino acid metabolism-particularly through pathways involving glutamine and branched-chain amino acids-plays a central role in tumor metabolic reprogramming and survival. Beyond enzymatic regulation, TRIM proteins exert non-canonical functions through epigenetic modulation and interactions with signaling networks. This review synthesizes current insights into the multifaceted roles of TRIM proteins in metabolic control and cell death, suggesting that ferroptosis may link TRIM proteins to lipid and amino acid metabolism, and highlights the connection between TRIM proteins and metabolic stress as a key area for future research.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"174 ","pages":"Article 156394"},"PeriodicalIF":11.9000,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Emerging roles of TRIM in metabolic regulation\",\"authors\":\"Jiaxing Wang , Qiangzhou Wang , Xinrui Li , Qingqing Cai , Yulin Bi , Chenyang Xu , Hao Bai , Lihong Gu , Guobin Chang , Shihao Chen\",\"doi\":\"10.1016/j.metabol.2025.156394\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Recent findings have broadened our understanding of the tripartite motif (TRIM) protein family, positioning these proteins as pivotal regulators of cellular metabolism and cell fate. Primarily functioning as versatile E3 ubiquitin ligases, TRIM proteins orchestrate key metabolic pathways—including glucose, lipid, and amino acid metabolism—through both ubiquitination-dependent and -independent mechanisms such as oligomerization and epigenetic modification. For example, TRIM38, TRIM11, and TRIM24 have been reported to modulate glycolytic flux and insulin signaling by targeting key glucose transporters and glycolytic enzymes, with effects on cancer metabolism and insulin responses in model systems. Similarly, TRIM21 and TRIM56 have been implicated in fatty acid synthesis, oxidation, and cholesterol balance, with potential relevance to fatty-liver conditions and atherosclerosis. Moreover, TRIM-mediated regulation of amino acid metabolism-particularly through pathways involving glutamine and branched-chain amino acids-plays a central role in tumor metabolic reprogramming and survival. Beyond enzymatic regulation, TRIM proteins exert non-canonical functions through epigenetic modulation and interactions with signaling networks. This review synthesizes current insights into the multifaceted roles of TRIM proteins in metabolic control and cell death, suggesting that ferroptosis may link TRIM proteins to lipid and amino acid metabolism, and highlights the connection between TRIM proteins and metabolic stress as a key area for future research.</div></div>\",\"PeriodicalId\":18694,\"journal\":{\"name\":\"Metabolism: clinical and experimental\",\"volume\":\"174 \",\"pages\":\"Article 156394\"},\"PeriodicalIF\":11.9000,\"publicationDate\":\"2025-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metabolism: clinical and experimental\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S002604952500263X\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolism: clinical and experimental","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S002604952500263X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Recent findings have broadened our understanding of the tripartite motif (TRIM) protein family, positioning these proteins as pivotal regulators of cellular metabolism and cell fate. Primarily functioning as versatile E3 ubiquitin ligases, TRIM proteins orchestrate key metabolic pathways—including glucose, lipid, and amino acid metabolism—through both ubiquitination-dependent and -independent mechanisms such as oligomerization and epigenetic modification. For example, TRIM38, TRIM11, and TRIM24 have been reported to modulate glycolytic flux and insulin signaling by targeting key glucose transporters and glycolytic enzymes, with effects on cancer metabolism and insulin responses in model systems. Similarly, TRIM21 and TRIM56 have been implicated in fatty acid synthesis, oxidation, and cholesterol balance, with potential relevance to fatty-liver conditions and atherosclerosis. Moreover, TRIM-mediated regulation of amino acid metabolism-particularly through pathways involving glutamine and branched-chain amino acids-plays a central role in tumor metabolic reprogramming and survival. Beyond enzymatic regulation, TRIM proteins exert non-canonical functions through epigenetic modulation and interactions with signaling networks. This review synthesizes current insights into the multifaceted roles of TRIM proteins in metabolic control and cell death, suggesting that ferroptosis may link TRIM proteins to lipid and amino acid metabolism, and highlights the connection between TRIM proteins and metabolic stress as a key area for future research.
期刊介绍:
Metabolism upholds research excellence by disseminating high-quality original research, reviews, editorials, and commentaries covering all facets of human metabolism.
Consideration for publication in Metabolism extends to studies in humans, animal, and cellular models, with a particular emphasis on work demonstrating strong translational potential.
The journal addresses a range of topics, including:
- Energy Expenditure and Obesity
- Metabolic Syndrome, Prediabetes, and Diabetes
- Nutrition, Exercise, and the Environment
- Genetics and Genomics, Proteomics, and Metabolomics
- Carbohydrate, Lipid, and Protein Metabolism
- Endocrinology and Hypertension
- Mineral and Bone Metabolism
- Cardiovascular Diseases and Malignancies
- Inflammation in metabolism and immunometabolism