BOTH NUCLEAR AND MITOCHONDRIAL CYTOCHROME-C-OXIDASE MESSENGER-RNA LEVELS INCREASE DRAMATICALLY DURING MOUSE POSTNATAL-DEVELOPMENT

The steady-state levels of 13 of 16 cytochrome c oxidase (COX) mRNAs and mitochondrial DNA were measured during the postnatal development of mouse skeletal muscle, ventricle, kidney and brain as well as during the differentiation of mouse myoblasts into myofibres in cell culture. These experiments indicate that large co-ordinated increases in COX mRNA levels and isoform switching are important for the elaboration of this enzyme during postnatal development and demonstrate the importance of gene-regulatory mechanisms in controlling COX activity. On a per nucleus basis, the level of the mitochondrial- and most nuclear-encoded COX mRNAs co-ordinately increase 3-10-fold during postnatal development, with the highest levels obtained in ventricle and skeletal muscle. However, concentrations of mitochondrial and nuclear COX mRNAs remain constant during the differentiation of myoblasts into fibres in cell culture. A gradual change from the liver to the heart isoform of COX subunit VIa mRNA occurs during postnatal development of skeletal muscle and ventricle and is nearly complete 3 days after the formation of myofibres in cell culture. Mitochondrial DNA increases proportionally with COX mRNAs during mouse postnatal development but not during myoblast differentiation in cell culture, in which mitochondrial DNA levels increase 5-fold and mitochondrial mRNA levels remain constant. This suggests that mitochondrial DNA replication may control mitochondrial RNA concentrations during postnatal development but not during myoblast differentiation in cell culture.