The Impact of Rhot1 and 2 on Cardiomyocyte Energetics and Survival

Rhot1 和 2 对心肌细胞能量和存活的影响

• 批准号: 469360875
• 负责人: Dr. Christian Riehle
• 金额: --
• 依托单位: Klinik für Kardiologie und Angiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/469360875?language=en
• 关键词: Impact; Rhot1; Cardiomyocyte; Energetics; Survival

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.

心脏对维持收缩功能有很高的能量需求。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。鉴于心肌组织的能量储存有限，ATP必须由心肌细胞线粒体持续产生。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，不断地受到有丝分裂的影响，有丝分裂是细胞器质量控制和循环以维持ATP生产的生物过程。线粒体质量控制的扰动会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(Rhot1)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异构体和线粒体运动对心脏能量学的影响以及心力衰竭的发生目前尚不清楚。我们的研究将为心肌细胞线粒体运动提供新的机制洞察力，并将确定Rhot异构体和线粒体运动介导心肌保护作用的机制。