La Traducció genètica mitocondrial i malalties associades

Abstract

In humans, as in the majority of eukaryotic organisms, protein synthesis occurs simultaneously in the cytoplasm and in those organelles that possess their own genome. Mitochondria require its own translational machinery in order to synthesize the 13 polypeptides, encoded in the mitochondrial genome, which are part of the respiratory chain and the oxidative phosphorylation complexes, responsible for supplying energy to the cell. The elements that compose this machinery are encoded both in the mitochondrial and the nuclear genome, and participate in gene translation in a coordinate manner. Mutations in genes that code for these factors of the gene translation apparatus trigger a wide range of severe pathologies in humans, characterized by heterogeneous symptoms that difficult their diagnostic and treatment. There exist human mitochondrial diseases caused by mutations in the mitochondrial DNA which specifically affect tRNA and rRNA and, additionally, mutations in nuclear encoded mitochondrial proteins have been described, among which are mutations in translation factors, enzymes involved in tRNA processing and modification, mitoribosomal proteins, and aminoacyl-tRNA synthetases. The complexity of mitochondrial pathologies, the variety of symptoms they cause, and the difficulty to manipulate mitochondrial DNA complicate the research related to these diseases and justify the generation of animal models that allow their characterization and the development of new therapeutic strategies.