Publication Details
Abstract
Objective: Mitochondrial diseases are a category of clinically diverse and difficult to diagnose disorders that are also challenging to treat. These disorders are caused by mutations of the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA), which encode mitochondrial and nuclear genes respectively. It is a complicated process in which these two genomes interact with some special genetic characteristics that determine the spectrum of clinical manifestations: the phenomenon of maternal inheritance, heteroplasmy, genetic bottleneck, makes the task of diagnosis a daunting endeavor. This review attempts to uncover the basic genetic concepts of the mitochondrial genome and the revolutionary role of bioinformatics and systems biology in the knowledge of mitochondrial pathology. Method: We explore the concept of the next-generation sequencing (NGS) technologies that have transformed the genetic diagnostics process, allowing to identify causative mutations fast. In addition, we discuss how multi-omics integration and computational modeling could be used to understand the complexity of molecular networks and pathways that are impaired in these diseases. Results: We demonstrate, using case study of particular mitochondrial diseases such as Leigh syndrome, Leber hereditary optic neuropathy (LHON) and mitochondrial cardiomyopathy, how such sophisticated methods are not only enhancing the accuracy of diagnosis but also leading to new treatment interventions. Novelty: Lastly, we explain the recent problems and perspectives of the field, with the prospects of a new era of personalized medicine to patients with mitochondrial disorders.