Project 458910

Heart failure affects over 600,000 Canadians, and there are very serious effects: over 50% of patients die within 5 years of diagnosis. Significant damage to the heart can lead to chronic symptoms including fatigue, persistent coughing, bodily swelling, and nausea. Underlying these clinical problems are changes in how the heart processes energy. Within cells, including heart cells, mitochondria -commonly called the cellular 'powerhouses' - are responsible for converting nutrients into an energy currency called adenosine triphosphate (ATP). The heart requires massive amounts of ATP to function (e.g., over 30kg every day), making mitochondria very important to heart health. During heart failure, mitochondria cannot produce enough ATP, so the heart struggles to pump blood throughout the body. Current treatments for heart failure reduce symptoms, but do not target the problems in mitochondria. An essential mitochondrial structural protein, optic atrophy protein-1 (OPA1), has recently been shown to increase mitochondrial energy efficiency and protect against heart failure. Our overall research goal is to study how this protein does this. We will study its function in controlling mitochondrial efficiency and protecting against heart failure. In normal mice and in mice with high levels of this protein, we will surgically induce heart failure and measure the activity of the heart's 'powerhouses' and cellular stress responses. As well, we will conduct many experiments in cultures of human heart cells with reduced levels of this protein to get detailed information about mechanisms. Ultimately, our research will lead to an improved understanding of how mitochondria play important roles in protection from heart failure. These findings may lead to the development of new types of medicines to prevent and treat heart failure.