Researcher(s)
- Dexter Matthews, Biological Sciences, University of Delaware
Faculty Mentor(s)
- Chi Keung Lam, Biological Sciences, University of Delaware
Abstract
The Effect of Hsp90b Knockout on Murine Myocardial Mitochondria
Heart disease is one of the most common causes of death in the United States regardless of gender or ethnicity. Disruption or dysregulation of multiple signaling pathways in the heart can cause fibrosis, hypertrophy, and cell death eventually leading to heart failure. An attractive target for treatment and prevention of heart disease is heat shock protein 90 (Hsp90) as it can interact with 10% of all cytosolic proteins, many of which facilitate signal transduction in the heart. Targeting Hsp90 may allow for simultaneous treatment of multiple pathways to help prevent the onset and development of heart failure. However current treatment options are limited due to a lack of full understanding on what specific proteins HSP90 effects. This is further compounded by the fact that there are multiple isoforms of HSP90 with little research done on each one’s role.
Previous studies from our lab demonstrate that one isoform, Hsp90beta plays a role in the mitochondria in the heart. This is important as mitochondria are responsible for energy production in the heart so any potential dysfunction could be significant. We aim to study HSP90beta by knocking out the protein in mouse cardiomyocytes using tamoxifen inducible Cre-Loxp system. Western blotting will be used to measure differences in protein expression for various mitochondrial proteins. Results show a significant decrease in proteins in the MICOS complex in the knockout mice. The MICOS complex is responsible for forming cristae in the inner mitochondrial membrane. From this we can conclude that HSP90beta interacts with the MICOS complex in mitochondria. This information could be used to help treat mitochondrial dysfunction in the heart, reducing a potential risk for heart disease.