The Impact of Rhot1 and 2 on Cardiomyocyte Energetics and Survival

心脏需要非常高的能量来维持收缩功能。人类心脏每天消耗多达30公斤的三磷酸腺苷（ATP），大约是其质量的100倍。由于心肌组织的能量储存有限，ATP必须由心肌细胞线粒体不断产生。因此，在哺乳动物的所有器官中，心脏的线粒体含量最高。线粒体是动态的细胞器，不断地进行线粒体自噬，这是一个细胞器质量控制和再循环以维持ATP生产的生物过程。线粒体自噬质量控制的扰动导致线粒体功能障碍和心力衰竭。我们的初步数据表明ras同源家族成员T (Rhot) 1和2具有心脏保护作用，这是细胞内线粒体运动所必需的。然而，Rhot亚型和线粒体运动对心脏能量学和心力衰竭发展的影响目前尚不清楚。我们的研究将为心肌细胞线粒体运动提供新的机制见解，并将确定Rhot亚型和线粒体运动介导心脏保护作用的机制。

The heart has a very high energy demand to maintain contractile function. The human heart consumes up to 30 kg of adenosine triphosphate (ATP) per day, or roughly 100 times its mass. Given the limited energy storage of cardiac tissue, ATP has to be constantly generated by cardiomyocyte mitochondria. Consequently, the heart has the greatest mitochondrial content of all organs in mammals. Mitochondria are dynamic organelles that are constantly subjected to mitophagy, a biological process of organelle quality control and recycling to maintain ATP production. Perturbations in mitophagic quality control results in mitochondrial dysfunction and heart failure. Our preliminary data suggest a cardioprotective role for ras homolog family member T (Rhot) 1 and 2, which are required for intracellular mitochondrial motility. However, the impact of Rhot isoforms and mitochondrial motility on cardiac energetics and the development of heart failure are currently not known. Our studies will provide new mechanistic insight into mitochondrial motility in cardiomyocytes and will determine the mechanisms by which Rhot isoforms and mitochondrial motility mediate cardioprotective effects.