Human mitochondrial transfer RNAs: role of pathogenic mutation in disease

The human mitochondrial genome encodes 13 proteins. All are subunits of the respiratory chain complexes involved in energy metabolism. These proteins are translated by a set of 22 mitochondrial transfer RNAs (tRNAs) that are required for codon reading. Human mitochondrial tRNA genes are hotspots for pathogenic mutations and have attracted interest over the last two decades with the rapid discovery of point mutations associated with a vast array of neuromuscular disorders and diverse clinical phenotypes. In this review, we use a scoring system to determine the pathogenicity of the mutations and summarize the current knowledge of structure-function relationships of these mutant tRNAs. We also provide readers with an overview of a large variety of mechanisms by which mutations may affect the mitochondrial translation machinery and cause disease.