心力衰竭是一种与线粒体功能障碍相关的能量代谢异常性疾病。既往研究显示死亡相关蛋白激酶DAPK参与调控线粒体功能，影响肿瘤等多种疾病进展，但其在心力衰竭中的作用尚不清楚。我们发现DAPK3在小鼠心脏中优势表达，心肌特异性DAPK3诱导敲除加重缺血性心衰恶化。在分子层面，我们发现DAPK3与线粒体代谢的关键调控分子ADP/ATP转运酶ANT1存在蛋白互作。由此，我们提出DAPK3缺失导致ANT1功能障碍，引起线粒体能量代谢紊乱，促进心力衰竭发展的科学假说。我们将采用小鼠缺血性心衰模型，评估DAPK3在缺血性心衰中对心功能和心肌能量代谢的影响；利用Seahorse系统，通过细胞基因敲除、过表达、靶分子阻断等方式，研究DAPK3对心肌细胞线粒体氧化磷酸化的调控作用与方式。探索DAPK3对心肌线粒体的调控作用与机制，明确其在心衰病程中的作用，为心力衰竭的研究提供了新的方向与可能。

Heart failure is considered as a kind of energy deprived disease related to mitochondrial dysfunction. Previous studies have shown that death associated protein kinase DAPK regulated mitochondrial function and played an important role in many diseases, such as cancer, but its role in heart failure is not clear. Our study found that DAPK3 was expressed preferentially in the heart of mice, and its deletion could lead to the deterioration of ischemic heart failure. We also found that there was protein interaction between DAPK3 and ANT1, a key molecule regulating mitochondrial metabolism. Therefore, we propose the hypothesis that the loss of DAPK3 leads to the dysfunction of mitochondrial ADP / ATP transporter ANT1, causing the disorder of mitochondrial energy metabolism and promotes the development of heart failure. We will use a mouse model of ischemic heart failure to evaluate the effect of DAPK3 on cardiac function and mitochondrial metabolism in heart failure. We will use the Seahorse system to study the regulatory effect of DAPK3 on mitochondrial oxidative phosphorylation of cardiomyocytes through gene knockout, overexpression and downstream effector interference. To explore the mechanism of DAPK3 regulating myocardial mitochondrial function and its role in heart failure provides a new direction and possibility for the study of heart failure.