Structural Basis for Mitochondrial Disease in Large Subunit (LSU) Assembly of Mitochondrial Ribosomes

Abstract: 

The mitochondria are a unique organelle, due to the fact that it possesses its own DNA and thus is involved in producing its own protein building blocks. The mitochondrial ribosomes play a key role in the protein synthesis mechanism of the organelle, meaning a dysfunction in the large or small subunits eventually impacts this process. Throughout the past decades, scientists and researchers have been monitoring the mitochondrial disease, its types and effects on the human organism. The mitochondrial DNA-related disorders are divided into two key groups: those resulting from mutations in genes encoding individual proteins of the respiratory chain, and those resulting from mutations in genes involved in mitochondrial protein synthesis. Among these, mutations in the mitochondrial translation apparatus, the mitochondrial ribosome structural components and assembly factors, cause mitochondrial diseases such as cardiomyopathy and protein synthesis deficiencies. The primary focus of this research work is the relationship between the mitochondrial disease and the large subunit assembly in mitochondrial ribosomes. Understanding the composition of the mitochondria, its DNA, and the mitochondrial ribosomes, and studying the protein synthesis and large subunit assembly from a structural perspective, the selected example of a mutation in the MRPL3 (uL3m) is extensively explored.