Molecules and Experimental Models in Mitochondrial Disorders

The life functions of eukaryotic cells are intricately regulated by mitochondria. Despite the long-standing reputation of these organelles as the “powerhouse” of cells, decades of mitochondrial research unveiled loads of novel tasks, many of which have turned out to be unrelated to bioenergetic metabolism [1]. Therefore, the functional complexity and the multifaceted nature of mitochondria make it difficult to clearly define their cellular role [2]. The synthesis of heme, ubiquinone, lipids, amino acids, steroid hormones, and Fe–S clusters are among the many anabolic processes that take place in mitochondria. Moreover, the import of macromolecules and the exchange of metabolites, nucleotides, membrane lipids, and ions with other subcellular compartments are just a few of the many cellular activities in which these organelles take part. Remarkably, as dynamic entities going through cycles of fission and fusion, mitochondria are able to adjust to changes in metabolism or cellular stress thanks to their structural transitions [3]. The mitochondria, which descend from bacterial endosymbionts, are also unique for having retained their genome. They possess sophisticated machineries for mtDNA replication and expression that rely on proteins encoded by nuclear genes [4]. Therefore, changes in mitochondrial functions and dynamics as well as mutations in both nuclear and mitochondrial genes involved in mtDNA metabolism cause a wide range of dysfunctions and syndromes, often referred to as mitochondrial diseases. In addition, severe metabolic and age-related pathologies (obesity, diabetes, Parkinson’s disease, and many more), as well as ageing itself, have been linked to mitochondrial dysfunction [5].