The contribution of mitochondria to cardiovascular physiology and pathology has been my primarily focus for many years. Heart failure (HF) is the leading cause of death in the US and a major reason for hospital readmissions among people over age 65, according to the American Heart Association. Energetic failure is considered an important pathogenic and potentially therapeutic element of HF, raising the need to examine the role of substrate utilization and mitochondrial function in HF. I lead several research projects which are aimed to find a pharmacological intervention for HF by enhancing mitochondrial function or shifting substrate preferences towards ketone bodies utilization. One project is designed to test the use of ketone esters as a pharmacological tool to enhance ketones utilization in heart failure in order to support impaired metabolism in HF without a need to adhere to strict ketogenic diets. The second project investigates whether fumarate-based drugs can prevent lethal cardiomyopathy in Friedreich's ataxia. Friedreich's ataxia is neurodegenerative movement disorder which places children and young adults in the wheelchairs by the time they graduate from high school. There is no treatment that cures this devastating disease, and most patients die from cardiomyopathy in their 30s. This lethal cardiomyopathy is caused by deficient expression of just one mitochondrial protein called frataxin. We synthesized a drug that shows cardiac protection in animal models of Friedreich's ataxia. My research is focusing on pharmacokinetics and pharmacodynamics of this novel drug, safety, toxicology, and the mechanisms of cardioprotective action.