NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly  

作　　者：Tingting Hou Rufeng Zhang Chongshu Jian Wanqiu Ding Yanru Wang Shukuan Ling Qi Ma Xinli Hu Heping Cheng Xianhua Wang 

机构地区：[1]State Key Laboratory of Membrane Biology,Beijing Key Laboratory of Cardiometabolic Molecular Medicine,Peking-Tsinghua Center for Life Sciences,Institute of Molecular Medicine,Peking University,Beijing 100871,China [2]State Key Laboratory of Space Medicine Fundamentals and Application,China Astronaut Research and Training Center,Beijing 100094,China

出　　处：《Cell Research》2019年第9期754-766,共13页细胞研究（英文版）

基　　金：We thank Ms. Yuli Liu for her kind help in echocardiogram test,Dr.Lin Pan and Ms. Dongwei Ma for their help in histological analysis, Drs. Liping Wei and Chuanyun Li for their help in bioinformatics analysis, Dr. Rongli Zhang and Ms.Saifang Yan for their help in IR experiments, and Drs. lain C. Bruce, Ruiping Xiao, Yingxian Li, and Yan Zhang for valuable comments.This work was supported by the National Key Basic Research Program of China (2017YFA0504000,2016YFA0500403 and 2013CB531200);the National Science Foundation of China (31670039,8182780030,31821091,and 31470811).

摘　　要：The impairment of mitochondrial bioenergetics,often coupled with exaggerated reactive oxygen species (ROS) production, is a fundamental disease mechanism in organs with a high demand for energy, including the heart. Building a more robust and safer cellular powerhouse holds the promise for protecting these organs in stressful conditions. Here, we demonstrate that NADH:ubiquinone oxidoreductase subunit AB1 (NDUFAB1), also known as mitochondrial acyl carrier protein, acts as a powerful cardio-protector by conferring greater capacity and efficiency of mitochondrial energy metabolism. In particular, NDUFAB1 not only serves as a complex I subunit, but also coordinates the assembly of respiratory complexes I, II, and III, and supercomplexes, through regulating iron-sulfur biosynthesis and complex I subunit stability. Cardiac-specific deletion of Ndufab1 in mice caused defective bioenergetics and elevated ROS levels, leading to progressive dilated cardiomyopathy and eventual heart failure and sudden death. Overexpression of Ndufab1 effectively enhanced mitochondrial bioenergetics while limiting ROS production and protected the heart against ischemia-reperfusion injury. Together, our findings identify that NDUFAB1 is a crucial regulator of mitochondrial energy and ROS metabolism through coordinating the assembly of respiratory complexes and supercomplexes, and thus provide a potential therapeutic target for the prevention and treatment of heart failure.

关 键 词：NDUFAB1 ROS RESPIRATORY complex 

分 类 号：Q[生物学]