title: Dietary isoflavone daidzein promotes Tfam expression that increases mitochondrial biogenesis in C2C12 muscle cells.
abstract: Mitochondrial dysfunction in muscles leads to a wide range of metabolic and age-related disorders. Recently, it has been reported that a natural polyphenol, resveratrol, affects mitochondrial biogenesis. This study aimed to identify other natural polyphenolic compounds that regulate mitochondrial biogenesis in muscles. For this purpose, we used the C2C12 murine muscle cell line. Screening involved a reporter assay based on the promoter of mitochondrial transcription factor A (Tfam). We found that several polyphenols exhibited the ability to increase Tfam promoter activity and that the soy isoflavone daidzein was a most potent candidate that regulated mitochondrial biogenesis. When C2C12 myotubes were treated with 25-50 μM daidzein for 24h, there were significant increases in the expression of Tfam and mitochondrial genes such as COX1 and Cytb as well as the mitochondrial content. Using several mutant Tfam promoter fragments, we found that the transcription factor, nuclear respiratory factor (NRF) and its coactivator, PGC1α, were necessary for the effect of daidzein on Tfam expression. Finally, silencing of sirtuin-1 (SIRT1) by shRNA resulted in inhibition of the daidzein effects on mitochondrial gene expression. In conclusion, daidzein regulates mitochondrial biogenesis in muscle cells by regulating transcriptional networks through a SIRT1-associated pathway. These results suggest that daidzein would be beneficial to protect against a wide range of diseases caused by muscle mitochondrial dysfunction.
authors.affiliation: Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo, Tokyo 112-8610, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Yoshino
authors.affiliation: Institute of Environmental Science for Human Life, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Naka
authors.affiliation: Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo, Tokyo 112-8610, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo, Tokyo 112-8610, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Shibasaki
authors.affiliation: Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo, Tokyo 112-8610, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Toh
authors.affiliation: Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo, Tokyo 112-8610, Japan.
authors.forename: Sakuka
authors.initials: S
authors.lastname: Tsukamoto
authors.affiliation: Institute of Environmental Science for Human Life, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Nutrition and Food Science, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo, Tokyo 112-8610, Japan. Electronic address: iida.kaoruko@ocha.ac.jp.
authors.forename: Kaoruko
authors.initials: K
authors.lastname: Iida
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D019587:Dietary Supplements; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006609:High Mobility Group Proteins / Q000235:genetics*; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism; D051265:NF-E2-Related Factor 1 / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D059808:Polyphenols / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D007529:Isoflavones; D051265:NF-E2-Related Factor 1; D059808:Polyphenols; C081930:Tfam protein, mouse; C004742:daidzein; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Daidzein; Mitochondria; Muscles; PGC1α; Sirtuin-1