Carlos Quintero

Helios Scholar

Leigh syndrome (LS) is a rare mitochondrial disease characterized by bilateral symmetrical lesions in high energy-demand neural regions such as the basal ganglia, cerebellum, brainstem, and thalamus. MTFMT is a nuclear-encoded enzyme that localizes to the mitochondria, catalyzing the formation of formylmethionyl-tRNA (fMet-tRNA) and initiating mitochondrial translation. Mutations in the MTFMT gene result in aberrant mitochondrial translation of OXPHOS complexes I, III, and IV. The subsequent impairment of ATP synthesis contributes to progressive neurodegeneration and the development of MTFMT LS. To develop a cell model system that accurately mimics the neuronal cell death and neural lesions in MTFMT LS, our research focuses on generating an in vitro model of this disease using patient-derived fibroblasts. By applying an optimized concentration of galactose to patient-derived fibroblasts, we biased the metabolic profile of these cells toward oxidative phosphorylation, simulating the stress conditions and neural lesions characteristic of MTFMT LS. The model developed in this study is readily manipulatable and replicable, fulfilling the unmet clinical need for a cell model system of MTFMT LS. Notably, this model serves as a valuable tool for future drug screening processes, allowing for the identification of compounds that can prevent or mitigate cell death pathways in LS and other mitochondrial diseases.