Methods and models for functional studies on mtDNA mutations

After 30 years of mitochondrial medicine, several models and methods for studying the pathogenic effects of mtDNA mutations have been developed. However, considering the difficulty to manipulate mtDNA, the possibility to obtain models for mitochondrial diseases remains challenging. Recently, the perspective to generate induced pluripotent stem cells from patients’ fibroblasts and differentiate them in specific cell populations or organoid has raised great interest for studying the molecular mechanisms of mitochondrial dysfunctions and for drug screening. Despite the technical hurdles, some animal models with mutations in mtDNA have been generated and represent valuable tools for the study of pathogenetic mechanisms and the test of new therapies. In parallel, biochemical methods for assessing mitochondrial function and efficiency are more and more sophisticated and developed on a small scale. Here, we summarize and discuss the different models and methods currently used to investigate the impact of mtDNA alterations on OXPHOS complexes function and structure.