Induced pluripotent stem cell-derived models for mtDNA diseases

Mitochondrial disease due to mutations in the mitochondrial DNA (mtDNA) is a common cause of human inherited disorders. Targeted modification of the mitochondrial genome has not succeeded with the current transgenic technologies. Furthermore, readily available cultured patient cells often do not manifest the disease phenotype. Therefore, pathogenic mechanisms underlying these disorders remain largely unknown, as the lack of model systems has hampered mechanistic studies. Stem cell technology has opened up new ways to use patient cells in research, through generation of induced pluripotent stem cells (iPSCs) and differentiation of these to disease-relevant cell types, including, for example, human neurons and cardiomyocytes. Here, we discuss the use of iPSC-derived models for disorders with mtDNA mutations.