Achim Paululat

Heart failure in flies and humans: A Drosophila model for human cardiomyopathies

Dysfunction of the heart is one of the most common causes of death in the Western world. An inherited form of heart malfunction is arrhythmogenic right ventricular cardiomyopathy (ARVC). A highly aggressive form of ARVC is subtype 5, caused by a mutation in the ER/SR transmembrane protein TMEM43. Male carriers of the mutation have an extremely high risk of dying from sudden cardiac death between the ages of 20-40. Together with human geneticists from the Heart and Diabetes Center in Bad Oeynhausen, we decipher the molecular basis of this cardiomyopathy, using Drosophila and human cells as models in a translational approach. I will provide the first evidence, that TMEM43 regulates energy homeostasis in mitochondria via ER-mitochondrial contact sites. TMEM43 may interact directly or indirectly with one of the major ion channels of mitochondria, VDAC, and controls membrane potential and accessibility of stored energy. 

Reference: Klinke, N., Meyer, H., Ratnavadivel, S., Reinhardt, M., Heinisch, J.J., Malmendal, A., Milting, H. and Paululat, A. (2022) A Drosophila melanogaster model for TMEM43 related Arrhythmogenic right ventricular cardiomyopathy type 5. Cellular and Molecular Life Sciences (Cell Mol Life Sci), 79(8):444. DOI: 10.1007/s00018-022-04458-0