Transient activation of mitochondrial translation regulates the expression of the mitochondrial genome during mammalian mitochondrial differentiation

José A. ENRíQUEZ; José M. CUEZVA; José M. IZQUIERDO; Julio MONTOYA; Luciana K. OSTRONOFF

摘要

pRegulation of the expression of the nuclear-encoded β-subunit of Hsup+/sup-ATP synthase (β-Fsub1/sub-ATPase) gene of oxidative phosphorylation during differentiation of liver mitochondria is mainly exerted at two post-transcriptional levels affecting both the half-life [Izquierdo, Ricart, Ostronoff, Egea and Cuezva (1995) J. Biol. Chem. b270/b, 10342–10350] and translational efficiency [Luis, Izquierdo, Ostronoff, Salinas, Santarén and Cuezva (1993) J. Biol. Chem. b268/b, 1868–1875] of the transcript. Herein, we have studied the expression of the mitochondrial (mt) genome during differentiation of rat liver mitochondria in an effort to elucidate the mechanisms of nucleo-mitochondrial cross-talk during biogenesis of the organelle. Estimation of the relative cellular representation of mt-DNA in liver reveals a negligible increase in mt-DNA copy number during organelle differentiation. Concurrently, the lack of changes in transcription rates of the mt-DNA ‘iin organello/i’, 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 revealed a transient 2-fold increase immediately after birth. Interestingly, the transient activation of mitochondrial translation at this stage of liver development is dependent on the synthesis of proteins in cytoplasmic polyribosomes. These findings support the hypothesis that the expression of nuclear and mitochondrial genes during biogenesis of mammalian mitochondria is developmentally regulated by a post-transcriptional mechanism that involves concerted translational control of both genomes./p

机译：> H + -ATP合酶（β-F_{1 -ATPase）基因核编码的β-亚基在分化过程中的表达调控肝线粒体主要在两个转录后水平起作用，影响半衰期[Izquierdo，Ricart，Ostronoff，Egea和Cuezva（1995）J.化学 270 ，10342–10350]和翻译效率[Luis，Izquierdo，Ostronoff，Salinas，Santarénand Cuezva（1993）J. Biol。着，第133-350页化学 268 ，1868–1875年）。本文中，我们研究了大鼠肝线粒体分化过程中线粒体（mt）基因组的表达，以阐明细胞器生物发生过程中核线粒体串扰的机制。肝中mt-DNA相对细胞表达的估计表明，细胞器分化过程中mt-DNA拷贝数的增加可忽略不计。同时，细胞器中mt-DNA' '的转录速率以及稳态水平的mt-DNA缺乏变化，表明细胞器分化不受增加的控制。 mt基因组的转录。然而，孤立的线粒体的翻译率显示出生后立即增加了两倍。有趣的是，在肝脏发育的这一阶段，线粒体翻译的瞬时激活取决于细胞质多核糖体中蛋白质的合成。这些发现支持以下假设：哺乳动物线粒体生物发生过程中核和线粒体基因的表达受转录后机制的调控，该机制涉及两个基因组的一致翻译控制。}

Transient activation of mitochondrial translation regulates the expression of the mitochondrial genome during mammalian mitochondrial differentiation

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