Paymon Sadat

Biallelic mutations in a nuclear gene encoding mitochondrial methionyl-tRNA formyltransferase (MTFMT) results in combined oxidative phosphorylation (OXPHOS) deficiency and Leigh syndrome (LS). This mutation causes exon 4 skipping and nonsense mediated decay, and it interrupts the synthesis of the Mitochondrial Methionyl tRNA Formyltransferase enzyme. This enzyme is responsible for adding a formyl group to the amino acid methionine, which mitochondria use to initiate translation of its proteins. In this study, we performed Blue Native polyacrylamide gel electrophoresis (BN-PAGE) and western blot analysis to determine how the absence of the MTFMT enzyme affects the translation of mitochondrial proteins and quantified mitochondrial proteins in mutated cells compared to wild type cells. Our results indicated that there is a reduced amount of translation of protein subunit belonging to OXPHOS Complex IV. This impairs the mitochondria’s ability to perform cellular respiration and is likely contributing to mitochondrial disease pathogenesis.