The Effects of Hsp90 on Mitochondrial Structure

• Dexter Matthews, Biological Sciences, University of Delaware

• Chi Keung Lam, Biological Sciences, University of Delaware

Dex Matthews

Poster Abstract

Heart disease is one of the most common causes of death in the United States regardless of gender or ethnicity.1  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.2 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.3 This is important as mitochondria are responsible for energy production in the heart so any potential dysfunction could be significant. Further efforts by our lab showed that it interacted with certain structural proteins in the mitochondria. We aim to study HSP90beta by knocking out the protein in mouse cardiomyocytes using tamoxifen inducible Cre-Loxp system. We used electron microscopy to view the mitochondria and measure any changes in the structure when HSP90beta was knocked out. From this we discovered that there were significant differences in the circularity, membrane width, and lacunarity between control mice and KO ones. From this we can conclude that the lack of Hsp90beta could lead to more mitochondrial fission, and more packing of cristae within the mitochondria. Which could help further reveal how HSP90beta could be used to treat heart disease.

Bibliography

1. “Https://Www.Cdc.Gov/Heartdisease/Facts.Htm.” CDC.Gov. May 15, 2023.
2. Roberts, Richard J., Logan Hallee, and Chi Keung Lam. “The Potential of Hsp90 in Targeting Pathological Pathways in Cardiac Diseases.” Journal of Personalized Medicine 11, no. 12 (December 2021): 1373. https://doi.org/10.3390/jpm11121373.
3. Lam, Chi Keung, Wen Zhao, Guan-Sheng Liu, Wen-Feng Cai, George Gardner, George Adly, and Evangelia G. Kranias. “HAX-1 Regulates Cyclophilin-D Levels and Mitochondria Permeability Transition Pore in the Heart.” Proceedings of the National Academy of Sciences of the United States of America 112, no. 47 (November 24, 2015): E6466–75. https://doi.org/10.1073/pnas.1508760112.