title: Nuclear respiratory factors 1 and 2 are upregulated in hearts from copper-deficient rats.
abstract: It is known that mitochondrial transcription factor A (mtTFA) plays a pivotal role in coordinating the expression of proteins in the nuclear and mitochondrial genomes as it pertains to mitochondrial biogenesis. Hearts from copper-deficient rats have elevated mtTFA levels compared to copper-adequate rats. This study evaluated whether two proteins that control activation of mtTFA by binding to its promotor, nuclear respiratory factors 1 (NRF-1) and 2 (NRF-2), are also upregulated prior to any upregulation of mtTFA. Long-Evans male rats were fed either copper-adequate or copper-deficient diets from weanling for periods of time up to 26 d. At d 26, mtTFA levels were elevated in the hearts from the copper-deficient rats, but not at earlier time points of 14, 18, and 22 d. However, NRF-1 and NRF-2 levels were increased at d 14 and 18, but not at the other two later time-points. These results revealed that the upregulation of mtTFA and mitochondrial biogenesis is preceded by upregulation of NRF-1 and NRF-2, which is consistent with the known molecular events controlling mitochondrial biogenesis in other systems.
authors.affiliation: Department of Human Nutrition and Food Management, The Ohio State University, Columbus 43210, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mao
authors.forename: D M
authors.initials: DM
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D003300:Copper / Q000172:deficiency*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051268:GA-Binding Protein Transcription Factor; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D009206:Myocardium / Q000378:metabolism*; D051265:NF-E2-Related Factor 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051264:Nuclear Respiratory Factors; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; D024101:Mitochondrial Proteins; D051265:NF-E2-Related Factor 1; C495632:Nfe2l1 protein, rat; D009687:Nuclear Proteins; D051264:Nuclear Respiratory Factors; D012333:RNA, Messenger; C489030:Tfam protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D003300:Copper; D004247:DNA