WBSCR16 Determines Metabolic Flexibility Via Regulating Mitochondrial 16S rRNA Maturation
WBSCR16 Determines Metabolic Flexibility Via Regulating Mitochondrial 16S rRNA Maturation
Abstract Mitochondria play significant roles in energy homeostasis by dissipating excess calories. However, the key proteins in mitochondrial govern metabolically flexibility remain poorly understand. Herein, we generated adipose specific Wbscr16-/-mice and cells, both of which exhibited a preference for fat utilization and displayed dramatic mitochondrial changes. We demonstrated that WBSCR16 is essential for the specific cleavage of 16S rRNA-tRNALeu, leading to the production of maturated 16S rRNA, which in turn controls mitochondrial large ribosomal assembly. Importantly, WBSCR16 was identified as a 16S rRNA-binding protein that directly interacts with RNase P subunit MRPP3. Furthermore, evidence showed that WBSCR16 ablation promotes energy wasting via lipid cycling in BAT, leading to excess energy expenditure and resistance to obesity. Conversely, cells and mice with WBSCR16 overexpression preferred to glucose utilization. These findings suggest that WBSCR16 is the key mitochondrial switch protein between glucose and lipid metabolism, making it a promising target for the development of fat busting drug.
Feng Yang、Zhang Chen、Zhao Zhiyun、Huang Guorui、Guo Wei、Ning Guang、Zhang Shengjie、Shi Yifan、Wang Jiqiu、Dong Zi
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiaotong University School of Medicine||National Research Center for Translational Medicine, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine
基础医学生物化学分子生物学
Feng Yang,Zhang Chen,Zhao Zhiyun,Huang Guorui,Guo Wei,Ning Guang,Zhang Shengjie,Shi Yifan,Wang Jiqiu,Dong Zi.WBSCR16 Determines Metabolic Flexibility Via Regulating Mitochondrial 16S rRNA Maturation[EB/OL].(2025-03-28)[2025-04-25].https://www.biorxiv.org/content/10.1101/2023.06.15.545185.点此复制
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