Abstract

A defining feature of the eukaryotic cell is compartmentalised genomes with distinct modes of expression, transmission and evolution. Animal mitochondria possess one of the most simplified genomes in cellular life that is essential for cell fitness. Despite the genome simplicity, the mechanisms coordinating mitochondrial gene expression remain significant outstanding biological questions. Over the last decade, the revolution in genetic diagnostics revealed defects to mitochondrial gene expression manifest as an exceptionally large group of heterogeneous diseases that differ in severity, age of onset and tissue specificity. In all cases, these diseases are associated with a quantitative reduction in the oxidative phosphorylation complexes because of impaired protein synthesis on mitochondrial ribosomes. However, the biochemical defect alone cannot account for the exceptional clinical presentations observed in patients. This suggests additional factors underpin the molecular pathogenesis. Research from my laboratory points to the key role post-transcriptional and co-translational quality control mechanisms play in the regulation of mitochondrial gene expression. The current focus of my research is to identify the molecular basis by which errors in mitochondrial gene expression are generated, recognised and resolved, and the importance of these mechanisms in human health and disease.