Mitochondrial transcription factor A is increased but expression of ATP synthase beta subunit and medium-chain acyl-CoA dehydrogenase genes are decreased in hearts of copper-deficient rats

The mechanism(s) by which impaired mitochondrial respiratory function and t he accumulation of lipid droplets and mitochondria in hearts of copper-defi cient rats occur remains unclear. It is not known whether specific componen ts of the regulatory pathway involved in mitochondrial biogenesis, such as mitochondrial transcription factor A (mtTFA) and nuclear respiratory factor s 1 and 2 (NRF-1 and NRF-2), are activated in copper deficiency. Little is known about gene expression of enzymes involved in fatty acid oxidation (FA O) in hearts of copper-deficient rats. Male weanling rats were fed copper-a dequate (CuA), copper-deficient (CuD) or pair-fed (CuP) diets for 5 wk. Mit ochondria and lipid droplet volume densities from electron micrographs were greater and there was an elevation in the mtTFA protein level in hearts of copper-deficient rats. DNA binding activities of NRF-1 and NRF-2 did not d iffer among the groups. Northern blot analysis of cardiac tissue revealed t hat transcripts of F1F0-ATP synthase subunit c were greater, but mRNA level s of ATP synthase beta subunit and the FAO enzyme, medium-chain acyl-CoA de hydrogenase (MCAD), were lower in hearts of copper-deficient rats. Long-cha in acyl-CoA dehydrogenase (LCAD) mRNA levels did not differ among treatment groups. These results suggest that certain components of the mitochondrial biogenesis program are activated in hearts of copper-deficient rats. F1F0- ATP synthase beta subunit and MCAD transcript levels remain low, which may contribute to impaired mitochondrial respiratory function, decreased fatty acid utilization and lipid droplet accumulation in hearts of copper-deficie nt rats.