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

Abstract

Regulation of the expression of the nuclear-encoded beta-subunit of H(+)-ATP synthase (beta-F1-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. 270, 10342-10350] and translational efficiency [Luis, Izquierdo, Ostronoff, Salinas, Santarén and Cuezva (1993) J. Biol. Chem. 268, 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 met-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 "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 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.

Mitochondrial differentiation and oxidative phosphorylation system capacity in rat embryo during placentation period

“…As a result, during the gestational days studied in the current work, the nuclear transcriptional signals involved in mitochondrial biogenesis could already be reduced and other post-transcriptional signals, such as increased mRNA stability and/or translational efficiency, would become available to keep the mitochondrial differentiation process active. Therefore, such regulation would be similar to what has previously been reported during the rat perinatal period (Luis et al 1993, Izquierdo et al 1995, Ostronoff et al 1996.…”

“…Mitochondriogenesis is a complex event, including both mitochondrial proliferation and differentiation processes (Izquierdo et al 1995, Ostronoff et al 1996, which takes place according to specific energy demands in response to several physiological conditions (Williams et al 1987, Pillar & Seitz 1997, including prenatal (May-Panloup et al 2005, Thundathil et al 2005 and postnatal developmental stages (Luis et al 1993, Izquierdo et al 1995, Ostronoff et al 1996. In middle pregnancy, rat embryo mitochondria undergo considerable morphofunctional changes (Mackler et al 1973, Shepard et al 1998, Yang et al 1998 coinciding with the switch from glycolytic to oxidative metabolism that takes place on gestational day 12 (Akazawa et al 1994, Shepard et al 1997, just when the placentary circulation is established and oxygen becomes more available to the embryo (Jollie 1986, Akazawa 2005.…”

A large-scale screening of the normalized mammalian mitochondrial gene expression profiles

“…the abundance of mtRNA transcripts) is a function of cell type and state, as well as of the metabolic/respiratory activity of the proband (Annex & Williams, 1990 ;Kagawa et al, 1999 ;Unami et al, 2004). Importantly, the replication and transcription of the mitochondrial genome depends on nuclear gene products, and posttranscriptional mechanisms play an important role in regulating mitochondrial expression (Ostronoff et al, 1996 ;Escriva et al, 1999;Wu et al, 2002). While the mtDNA/mitochondrion ratio is essentially constant in all cell types in mammalian species, the number of mitochondria per cell and the amount of mtDNA per cell seem to be closely regulated within a given cell type but differ widely between cell types (Robin & Wong, 1988).…”

Development and Age-associated Differences in Electron Transport Potential and Consequences for Oxidant Generation

“…However, it is known that factors other than COX 1 mRNA abundance determine COX activity. In fact, control of mitochondrial protein levels is often at a translational or post-translational rather than a transcriptional level (76,77). For example, the peptide encoded by COX 1 is rate-limiting to complex IV assembly (78 -80).…”