title: Concise Review: Heteroplasmic Mitochondrial DNA Mutations and Mitochondrial Diseases: Toward iPSC-Based Disease Modeling, Drug Discovery, and Regenerative Therapeutics.
abstract: Mitochondria contain multiple copies of their own genome (mitochondrial DNA; mtDNA). Once mitochondria are damaged by mutant mtDNA, mitochondrial dysfunction is strongly induced, followed by symptomatic appearance of mitochondrial diseases. Major genetic causes of mitochondrial diseases are defects in mtDNA, and the others are defects of mitochondria-associating genes that are encoded in nuclear DNA (nDNA). Numerous pathogenic mutations responsible for various types of mitochondrial diseases have been identified in mtDNA; however, it remains uncertain why mitochondrial diseases present a wide variety of clinical spectrum even among patients carrying the same mtDNA mutations (e.g., variations in age of onset, in affected tissues and organs, or in disease progression and phenotypic severity). Disease-relevant induced pluripotent stem cells (iPSCs) derived from mitochondrial disease patients have therefore opened new avenues for understanding the definitive genotype-phenotype relationship of affected tissues and organs in various types of mitochondrial diseases triggered by mtDNA mutations. In this concise review, we briefly summarize several recent approaches using patient-derived iPSCs and their derivatives carrying various mtDNA mutations for applications in human mitochondrial disease modeling, drug discovery, and future regenerative therapeutics.
authors: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors: Hideyuki
authors: H
authors: Hatakeyama
authors: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.|Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors: Yu-Ichi
authors: Y
authors: Goto
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D015316:Genetic Therapy; D054629:Genome, Mitochondrial / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009154:Mutation; D010361:Patients
chemical_list: D004272:DNA, Mitochondrial
keywords: Induced pluripotent stem cells-based cellular disease model; Mitochondrial DNA mutation; Mitochondrial disease; Mitochondrial rejuvenation/maturation; Regenerative medicine