Abstract 1569 Elucidating the role of disease-associated mitochondrial factor Mdm38/LETM1

Mitochondria, the "powerhouse of the cell," are complex, highly dynamic organelles that rely on multilayered maintenance machinery for sustained functioning. One such mechanism includes ion exchange processes necessary for proper mitochondrial osmotic balance- known as ion homeostasis-which ensures the organelle's functional integrity and optimal energy production process. In baker's yeast, a well-established genetic model to study mitochondrial functions- the inner mitochondrial (IM) protein Mdm38 has been postulated to play a role in both membrane protein homeostasis and K+/H+ ion exchange. Lack of Mdm38 causes a significant decrease in the mitochondrial membrane potential and altered vacuolar morphology. The human homolog of Mdm38, LETM1, has been considered an essential gene. Mutations in LETM1 have been linked to multi-systemic disorders such as Wolf-Hirschhorn Syndrome. In addition, changes in cellular levels and functionality of LETM1 are associated with obesity, tumor development, and seizures. However, surprisingly little is known about the precise molecular roles of Mdm38 and LETM1. Therefore, this project aims to determine how exactly Mdm38 functions in the maintenance of IM homeostasis. This research focuses on identifying the optimal epitope tag for constructing the tagged version of the protein and further biochemical analysis of the Mdm38 complex including its behavior in response to defects in the mitochondrial protein quality control factors. This project is deepening our understanding of the molecular links between mitochondrial ion homeostasis and quality control- two mechanisms that are critical for normal mitochondrial function and cellular well-being. I want to express my gratitude to ASBMB for the Student Chapter Travel Award and to the IANR ARD Student Research Program for funding the research. I greatly appreciate Dr. Khalimonchuk for being my mentor and Dr. Bohovych for all the help in the lab.