Nuclear respiratory factors 1 and 2 are upregulated in hearts from copper-deficient rats

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.