TY - JOUR T1 - NDUFAB1 Protects Heart by Coordinating Mitochondrial Respiratory Complex and Supercomplex Assembly JF - bioRxiv DO - 10.1101/302281 SP - 302281 AU - Tingting Hou AU - Rufeng Zhang AU - Chongshu Jian AU - Wanqiu Ding AU - Yanru Wang AU - Qi Ma AU - Xinli Hu AU - Heping Cheng AU - Xianhua Wang Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/04/16/302281.abstract N2 - The impairment of mitochondrial bioenergetics, often coupled with exaggerated reactive oxygen species (ROS) production, is emerging as a common mechanism in diseases of organs with a high demand for energy, such as the heart. Building a more robust cellular powerhouse holds promise for protecting these organs in stressful conditions. Here, we demonstrate that NDUFAB1 (NADH:ubiquinone oxidoreductase subunit AB1), acts as a powerful cardio-protector by enhancing mitochondrial energy biogenesis. In particular, NDUFAB1 coordinates the assembly of respiratory complexes I, II, and III and supercomplexes, conferring greater capacity and efficiency of mitochondrial energy metabolism. Cardiac-specific deletion of Ndufab1 in mice caused progressive dilated cardiomyopathy associated with defective bioenergetics and elevated ROS levels, leading to heart failure and sudden death. In contrast, transgenic overexpression of Ndufab1 effectively enhanced mitochondrial bioenergetics and protected the heart against ischemia-reperfusion injury. Our findings identify NDUFAB1 as a central endogenous regulator of mitochondrial energy and ROS metabolism and thus provide a potential therapeutic target for the treatment of heart failure and other mitochondrial bioenergetics-centered diseases. ER -