Organelle-Specific Proteomic Profiling to Elucidate Mitochondrial Dysfunction and Therapeutic Mitochondrial Transfer in Friedreich’s Ataxia

Dr. Gomez-Ospina proposes to study how frataxin deficiency alters mitochondrial function in Friedreich’s ataxia (FRDA) at the level of specific cell types and organelles. Current proteomic studies lack the resolution to capture mitochondrial-specific changes, leaving critical disease mechanisms unclear. This project will use advanced technologies to profile proteins and metabolites within mitochondria isolated from FRDA cells. Using CRISPR/Cas9 genome editing, the team will tagged mitochondria in human lymphoblastoid and induced pluripotent stem cell (hiPSC) lines. These hiPSCs will be differentiated into cardiomyocytes and neurons—the two most vulnerable cell types in FRDA. Tagged mitochondria will be purified and analyzed to identify disease-associated changes in mitochondrial protein networks. In parallel, Dr. Gomez-Osina will test whether healthy mitochondria can be transferred from donor macrophages to FRDA cardiomyocytes and restore their function. Comparative proteomic analysis will determine if transferred mitochondria integrate and repair dysregulated networks. This approach could uncover mechanisms of mitochondrial dysfunction and evaluate mitochondrial transfer as a potential therapeutic strategy.