The Impact of Rhot1 and 2 on Cardiomyocyte Energetics and Survival

• Applicant: Dr. Christian Riehle
• Subject Area: Cardiology, Angiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 469360875

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.

• DFG Programme: Research Grants