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.

Subcellular mRNA localization has emerged as a mechanism for regulation of gene expression and protein-sorting pathways. Here we describe the different cytoplasmic presentation in rat hepatocytes of two nuclear mRNA species encoding subunits alpha and beta of the mitochondrial F1-ATPase complex. alpha-F1-ATPase mRNA is dispersed and scattered in the cytoplasm. In contrast, beta-F1-ATPase mRNA appears in rounded electron-dense clusters, often in close proximity to mitochondria. Hybridization experiments with beta2-microglobulin and beta-actin cDNA species reveal an expected subcellular distribution pattern of the mRNA species and a non-clustered appearance. Development does not alter the presentation of beta-F1-ATPase mRNA hybrids, although it affects the relative abundance of beta-F1-ATPase mRNA clusters in the cytoplasm of the hepatocyte. These findings illustrate in vivo the existence of two different sorting pathways for the nuclear-encoded mRNA species of mitochondrial proteins. High-resolution immunocytochemistry and immunoprecipitation experiments allowed the identification of the beta-subunit precursor in the cytoplasm of the hepatocyte, also suggesting a post-translational import pathway for this precursor protein. It is suggested that the localization of beta-F1-ATPase mRNA in a subcellular structure of the hepatocyte might have implications for the control of gene expression at post-transcriptional levels during mitochondrial biogenesis in mammals.