Changing patterns of transcriptional and post-transcriptional control of beta-F1-ATPase gene expression during mitochondrial biogenesis in liver.

To elucidate the mechanisms that regulate the expression of nuclear genes during biogenesis of mammalian mitochondria, the expression pattern of the beta-subunit of the ATP synthase gene has been characterized in rat liver between day 20 in utero and 12 weeks postnatal. The parallelism existing between transcriptional activity of the gene and the amount of beta-F1-ATPase protein in liver indicates that proliferation of mitochondria is controlled at the transcriptional level. On the other hand, an increased stability (4-5-fold) of beta-F1-ATPase mRNA during early neonatal life as well as a rapid postnatal activation of translation rates affecting mitochondrial proteins appear to control mitochondrial differentiation. Immunoelectron microscopy of the F1-ATPase complex during liver development revealed that the rapid postnatal increase in the in vivo rate of F1-ATPase synthesis was mostly used for functional differentiation of pre-existing organelles (Valcarce, C., Navarrete, R. M., Encabo, P., Loeches, E., Satrústegui, J., and Cuezva, J. M. (1988) J. Biol Chem. 263, 7767-7775). The findings support that beta-F1-ATPase mRNA decay is developmentally regulated in liver, indicating that gene expression is also controlled at this level during physiological transitions that affect biogenesis of mitochondria.