Translation mitochondrial protein

Mitochondrial DNA is inherited maternally. What makes mitochondrial diseases particularly interesting from a genetic point of view is that the mitochondrion has its own DNA (mtDNA) and its own transcription and translation processes. The mtDNA encodes only 13 polypeptides nuclear DNA (nDNA) controls the synthesis of 90-95% of all mitochondrial proteins. All known mito-chondrially encoded polypeptides are located in the inner mitochondrial membrane as subunits of the respiratory chain complexes (Fig. 42-3), including seven subunits of complex I the apoprotein of cytochrome b the three larger subunits of cytochrome c oxidase, also termed complex IV and two subunits of ATPase, also termed complex V. 

Mitochondrial proteins encoded by nuclear genes are translated by ribosomes free in the cytoplasm, then folded and transferred into the mitochondria by different molecular chaperones. 

Some Mitochondrial Proteins Are Transported after Translation... 

Mutations in tRNALeu n UR) may be expected to have an important effect on protein synthesis in mitochondria. The MELAS-associated human mitochondrial tRNALeu <[ UR) mutation causes aminoacylation deficiency and a concomitant defect in translation initiation (Borner et al., 2000). The expected result would be a deficit in general mitochondrial protein synthesis with resulting deficiencies of multiple OXPHOS components. Patients with MELAS disorder have been found to have a marked decrease in the activity of respiratory Complex I with a secondary reduction in the activity of Complex IV... 

Chloramphenicol inhibits mRNA translation by the 70S ribosomes of prokaryotes, but does not affect 80S eukaryotic ribosomes. Most mitochondrial proteins are encoded by... 

Mitochondria and chloroplasts are the two main eukaryotic cellular organelles that contain their own genome and undertake the semi-independent processes of transcription and translation. Most of the constituent proteins of these organelles are imported from the surrounding cytoplasm, but each organelle also synthesizes its own proteins. Here we shall limit our discussion to mitochondrial protein synthesis, because the chloroplast is not present in animal cells. 

Ostrander, D. B., et al. 2001. Lack of mitochondrial anionic phospholipids causes an inhibition of translation of protein components of the electron transport chain a yeast genetic model system for the study of anionic phospholipid function in mitochondria. J. Biol. Chem. 276 25262-25272. 

Until recently, the only deviations from the genetic code in eukaryotes were found in mitochondria and chloroplast, where some codons are different and the wobble position is even more flexible (mitochondria use only 24 types of tRNA to translate 13 mitochondrial proteins). However, three phenomenon, translational frameshifting, RNA editing, and protein splicing, remind us that nature is full of surprises. 

The surprising consequence of the lack of PG and CL in yeast is the lack of translation of mRNAs of four mitochondria-encoded proteins (cytochrome b and cytochrome c oxidase subunits I-III) as well as cytochrome c oxidase subunit IV [13] that is nuclear encoded. These results indicate that some aspects of translation of a subset of mitochondrial proteins (those associated with electron transport complexes in the inner membrane but not ATP metabolism) require PG and/or CL. 

Many papers deal with changes of the activities of mitochondrial enzymes in mammalian and other embryos (e.g., Greenfield and Boell, 1968, 1970 Weber and Boell, 1962) and are discussed in Chapter 9, this volume. Here we restrict ourselves to either mitochondrial protein synthesis in vitro or to in vivo experiments on the synthesis of mitochondrial enzymes involving the mitochondrial translation apparatus. 

Among the cytoplasmic petite p mutants there exists a class, the so-called low-density, or high-A,T petites with such severe alterations in their mtDNA as to render any extensive role for it in the transmission and specification of genetic information impossible, or at least highly unlikely, (e.g., refs. 4, 7, 41). What is the significance of this observation Simply this, that these mutants not only are incapable of mitochondrial protein synthesis—as are p mutants in general—and, hence, of translating any... 

In all our studies on this diverse range of systems, we have been led back at some stage to the properties and function of the mitochondrial membrane. Seen in retrospect, this is not surprising, as the products of the mitochondrial protein-synthesizing system are all components of the inner mitochondrial membrane, and the mitochondrial replication, transcription, and translation systems are all inner-membrane-associated to some extent. 

Analysis of the amino acid composition of the mitochondrially synthesized subunits of cytochrome oxidase of the rutamycin-sensitive ATP-ase (another membrane component which requires mitochondrial protein synthesis for some of its component polypeptides) and cytochrome b displayed a high proportion of nonpolar amino acid residues. The resulting unusually hydrophobic composition explains their insolubility in aqueous solutions. This hydrophobic character of the mitochondrially translated polypeptides may have relevance for speculations on the existence of mitochondrial protein synthesis. It has been suggested that their hydro-phobic properties make it necessary that these polypeptides be delivered to the inner mitochondrial membrane from the matrix side, since they cannot be transported through the cytoplasm and the intercristae space. 

It was of interest to determine the effects of the petite-inducing conditions described above on mitochondrial inner-membrane proteins, and, in particular, on products of mitochondrial protein synthesis. The efficient and quantitative production of petites at 18°C affords a special opportunity to examine the fate of mitochondrial translation products during the course... 

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