Functional studies to identify novel therapies for Mitochondrial Disease in Patients with methionyl-tRNA formyltransferase (MTFMT) mutation
Nuclear-encoded MTFMT formylate the Met-tRNAMet necessary for the initiation of translation in the mitochondria. In Homo sapiens, a single MTFMT-formylated-tRNA acts as both an initiator and elongator for protein synthesis. This process is critical for the synthesis of 13 mitochondrially-encoded proteins in complexes I, III and IV of the electron transport chain (ETC). Mutation in MTFMT gene has been associated with mitochondrial disease (oxidative phosphorylation deficiencies due to a decreased expression of MTFMT), Leigh syndrome, and developmental delay. At the Center for Rare Childhood Disorders (C4CRD), we have identified splice-site mutation at c.626C<T (chr. 15 exon 4) in the MTFMT gene from three patients with mitochondrial disease from two unrelated families. My work is focused on studying the mitochondrial biology through gene expression assays and western blot analysis. We also aimed to characterize the impact of MTFMT mutation in homozygous and heterozygous patient-derived fibroblasts and further plan on testing potential oligotherapie moving forward.