TRANSIENT ACTIVATION OF MITOCHONDRIAL TRANSLATION REGULATES THE EXPRESSION OF THE MITOCHONDRIAL GENOME DURING MAMMALIAN MITOCHONDRIAL DIFFERENTIATION

Regulation of the expression of the nuclear-encoded beta-subunit of H-ATP synthase (beta-F-1-ATPase) gene of oxidative phosphorylation duri ng differentiation of liver mitochondria is mainly exerted at two post -transcriptional levels affecting both the half-life [Izquierdo, Ricar t, Ostronoff, Egea and Cuezva (1995) J. Biol. Chem. 270, 10342-10350] and translational efficiency [Luis, Izquierdo, Ostronoff, Salinas, San taren and Cuezva (1993) J. Biol. Chem. 268, 1868-1875] of the transcri pt. Herein, we have studied the expression of the mitochondrial (mt) g enome during differentiation of rat liver mitochondria in an effort to elucidate the mechanisms of nucleo-mitochondrial cross-talk during bi ogenesis of the organelle. Estimation of the relative cellular represe ntation of mt-DNA in liver reveals a negligible increase in mt-DNA cop y number during organelle differentiation. Concurrently, the lack of c hanges in transcription rates of the mt-DNA 'in organello', as well as in steady-state levels of the mt-transcripts, suggests that organelle differentiation is not controlled by an increase in transcription of the mt-genome. However, translation rates in isolated mitochondria rev ealed a transient 2-fold increase immediately after birth. Interesting ly, the transient activation of mitochondrial translation at this stag e of liver development is dependent on the synthesis of proteins in cy toplasmic polyribosomes. These findings support the hypothesis that th e expression of nuclear and mitochondrial genes during biogenesis of m ammalian mitochondria is developmentally regulated by a post-transcrip tional mechanism that involves concerted translational control of both genomes.