Caloric Restriction Induces MicroRNAs to Improve Mitochondrial Proteostasis
Ran Zhang,
Xu Wang,
Jia-Hua Qu,
Bing Liu,
Peng Zhang,
Tao Zhang,
Peng-Cheng Fan,
Xiao-Man Wang,
Guang-Yuan Xiao,
Ye Su,
Yan Xie,
Yue Liu,
Jian-Fei Pei,
Zhu-Qin Zhang,
De-Long Hao,
Ping Xu,
Hou-Zao Chen,
De-Pei Liu
Affiliations
Ran Zhang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Xu Wang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Jia-Hua Qu
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Bing Liu
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Peng Zhang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Tao Zhang
State Key Laboratory of Proteomics, National Centre for Protein Sciences Beijing, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, Beijing Institute of Radiation Medicine, Beijing 102206, P.R. China
Peng-Cheng Fan
State Key Laboratory of Proteomics, National Centre for Protein Sciences Beijing, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, Beijing Institute of Radiation Medicine, Beijing 102206, P.R. China
Xiao-Man Wang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Guang-Yuan Xiao
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Ye Su
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Yan Xie
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Yue Liu
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Jian-Fei Pei
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Zhu-Qin Zhang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
De-Long Hao
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China
Ping Xu
State Key Laboratory of Proteomics, National Centre for Protein Sciences Beijing, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, Beijing Institute of Radiation Medicine, Beijing 102206, P.R. China
Hou-Zao Chen
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China; Corresponding author
De-Pei Liu
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P.R. China; Corresponding author
Summary: Both caloric restriction (CR) and mitochondrial proteostasis are linked to longevity, but how CR maintains mitochondrial proteostasis in mammals remains elusive. MicroRNAs (miRNAs) are well known for gene silencing in cytoplasm and have recently been identified in mitochondria, but knowledge regarding their influence on mitochondrial function is limited. Here, we report that CR increases miRNAs, which are required for the CR-induced activation of mitochondrial translation, in mouse liver. The ablation of miR-122, the most abundant miRNA induced by CR, or the retardation of miRNA biogenesis via Drosha knockdown significantly reduces the CR-induced activation of mitochondrial translation. Importantly, CR-induced miRNAs cause the overproduction of mtDNA-encoded proteins, which induces the mitochondrial unfolded protein response (UPRmt), and consequently improves mitochondrial proteostasis and function. These findings establish a physiological role of miRNA-enhanced mitochondrial function during CR and reveal miRNAs as critical mediators of CR in inducing UPRmt to improve mitochondrial proteostasis. : Biological Sciences; Molecular Biology; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Molecular Biology, Cell Biology, Functional Aspects of Cell Biology
