DEAD-box helicase 17(DDX17)protects cardiac function by promoting mitochondrial homeostasis in heart failure  

作　　者：Mingjing Yan Junpeng Gao Ming Lan Que Wang Yuan Cao Yuxuan Zheng Yao Yang Wenlin Li Xiaoxue Yu Xiuqing Huang Lin Dou Bing Liu Junmeng Liu Hongqiang Cheng Kunfu Ouyang Kun Xu Shenghui Sun Jin Liu Weiqing Tang Xiyue Zhang Yong Man Liang Sun Jianping Cai Qing He Fuchou Tang Jian Li Tao Shen 

机构地区：[1]The Key Laboratory of Geriatrics,Beijing Institute of Geriatrics,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing Hospital/National Center of Gerontology of National Health Commission,Beijing 100730,China [2]Peking University Fifth School of Clinical Medicine,Beijing 100730,China [3]Department of Laboratory Medicine,Huashan Hospital,Shanghai Medical College,Fudan University,Shanghai 200040,China [4]Biomedical Pioneering Innovation Center,School of Life Sciences,Peking University,Beijing 100871,China [5]Emergency Center,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [6]Department of Cardiology,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China [7]Graduate School of Peking Union Medical College,Beijing 100730,China [8]Department of Health Care,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100730,China [9]Peking-Tsinghua Center for Life Sciences,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China [10]Department of Pathology and Pathophysiology and Department of Cardiology at Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [11]Department of Cardiovascular Surgery,Peking University Shenzhen Hospital,Shenzhen 518036,China [12]Experimental Technology Center for Life Sciences at Beijing Normal University,Beijing 100875,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第6期2774-2790,共17页信号转导与靶向治疗（英文）

基　　金：supported by grants from the National Key R&D Program of China(2021YFE0114200,2018YFC2000100);the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2021-I2M-1-050);the Project funded by China Postdoctoral Science Foundation(2023M732704);the National Natural Science Foundation of China(81770228,82370584,81470427 and U23A20470);the Beijing Natural Science Foundation(7232141,7212086);the Beijing Hospital Clinical Research 121 Project(121-2016004);the National High Level Hospital Clinical Research Funding(BJ-2021-199,BJ-2023-156,BJ-2019-159).

摘　　要：DEAD-box helicase 17(DDX17)is a typical member of the DEAD-box family with transcriptional cofactor activity.Although DDX17 is abundantly expressed in the myocardium,its role in heart is not fully understood.We generated cardiomyocyte-specific Ddx17-knockout mice(Ddx17-cKO),cardiomyocyte-specific Ddx17 transgenic mice(Ddx17-Tg),and various models of cardiomyocyte injury and heart failure(HF).DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury.Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis,leading to progressive cardiac dysfunction,maladaptive remodeling and progression to heart failure.Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions.Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6(BCL6)and inhibit the expression of dynamin-related protein 1(DRP1).When DDX17 expression is reduced,transcriptional repression of BCL6 is attenuated,leading to increased DRP1 expression and mitochondrial fission,which in turn leads to impaired mitochondrial homeostasis and heart failure.We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure.These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

关 键 词：DDX17 HOMEOSTASIS cardiac 

分 类 号：R541.6[医药卫生—心血管疾病]