title: Low dose resveratrol ameliorates mitochondrial respiratory dysfunction and enhances cellular reprogramming.
abstract: Mitochondrial disease is associated with a wide variety of clinical presentations, even among patients carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, probably because of variations in mutant mtDNA proportions at the tissue and organ levels. Although several case reports and clinical trials have assessed the effectiveness of various types of drugs and supplements for the treatment of mitochondrial diseases, there are currently no cures for these conditions. In this study, we demonstrated for the first time that low dose resveratrol (RSV) ameliorated mitochondrial respiratory dysfunction in patient-derived fibroblasts carrying homoplasmic mtDNA mutations. Furthermore, low dose RSV also facilitated efficient cellular reprogramming of the patient-derived fibroblasts into induced pluripotent stem cells, partly due to improved cellular viability. Our results highlight the potential of RSV as a new therapeutic drug candidate for the treatment of mitochondrial diseases.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University, School of Medicine, Tokyo 160-0016, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mizuguchi
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. Electronic address: hideyuki@ncnp.go.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hatakeyama
authors.affiliation: Department of Obstetrics and Gynecology, Keio University, School of Medicine, Tokyo 160-0016, Japan.
authors.forename: Kou
authors.initials: K
authors.lastname: Sueoka
authors.affiliation: Department of Obstetrics and Gynecology, Keio University, School of Medicine, Tokyo 160-0016, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan; Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. Electronic address: goto@ncnp.go.jp.
authors.forename: Yu-Ichi
authors.initials: YI
authors.lastname: Goto
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D019069:Cell Respiration / Q000187:drug effects*; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol
keywords: Mitochondrial disease; Mitochondrial respiratory dysfunction; Patient-derived induced pluripotent stem cells (iPSCs); Resveratrol