Mitochondria protein translation

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. 

They may enter the cytosol and fold quickly into a compact form. This may require only a few seconds, whereas the translation process in the ribosome may take many seconds. The folding will therefore be cotranslational.525 Depending upon the N-terminal signal peptide the protein may later unfold and pass through a membrane pore or translocon into the endoplasmic reticulum (ER), a mitochondrion, chloro-plast, or peroxisome. Wherever it is, it will be crowded together with thousands of other proteins. It will interact with many of these, and evolution will have enabled some of these to become chaperones (discussed in Chapter 10).526... 

The oxidative phosphorylation system contains over 80 polypeptides. Only 13 of them are encoded by mtDNA, which is contained within mitochondria, and all the other proteins that reside in the mitochondrion are nuclear gene products. Mitochondria depend on nuclear genes for the synthesis and assembly of the enzymes for mtDNA replication, transcription, translation, and repair (Tl). The proteins involved in heme synthesis, substrate oxidation by TCA cycle, degradation of fatty acids by /i-oxidalion, part of the urea cycle, and regulation of apoptosis that occurs in mitochondria are all made by the genes in nuclear DNA. 

Chloramphenicol blocks translation in bacteria by inhibiting peptidyltransferase of the large ribosomal subunit. It does not interfere with peptidyltransferase in the large subunit of eukaryotic ribosomes. However, the mitochondrion of animal cells contains ribosomes that are similar to bacterial ribosomes, and chloramphenicol can block protein synthesis in this organelle. This could contribute to the side effects of this drug when used in the treatment of animals. 

There are also inhibitors that affect enzyme synthesis. Inhibitors of transcription (e.g., dibromothymoquinone [DBMIB]) and inhibitors of translation (e.g., cyclo-heximide [CHX]) are available but these are not specific to particular enzymes. In addition, because protein synthesis takes place within the chloroplast and mitochondrion in eukaryotes, prokaryotic protein synthesis inhibitors (e.g., chloramphenicol [CAP]) may be necessary to distinguish prokaryotic versus eukaryotic activity (e.g., Segovia and Berges, 2005). 

All three respiratory complexes are typical integral membrane proteins that span the inner mitochondrial membrane. Each consists of several different subunits, the exact number of which is still under debate. The genes of some subunits of cytochrome oxidase and the />c, complex are in mitochondrial DNA (mtDNA). These proteins are synthesised inside the mitochondrion. However, most proteins of these complexes, as well as cytochrome c, are synthesised on cytoplasmic ribosomes and coded by the nuclear genome. This raises intriguing questions of how the latter are imported into the mitochondrion and inserted into the mitochondrial membrane, as well as of how mitochondrial and cytoplasmic transcription and translation are synchronised [3-5]. 

As far as Is known, all RNA transcripts of mtDNA and their translation products remain In the mitochondrion, and all mtDNA-encoded proteins are synthesized on mitochondrial ribosomes. Mitochondria encode the rRNAs that form mitochondrial ribosomes, although all but one or two of the rl-bosomal proteins (depending on the species) are imported from the cytosol. In most eukaryotes, all the tRNAs used for protein synthesis in mitochondria are encoded by mtDNAs. However, In wheat, in the parasitic protozoan Trypanosoma brucei (the cause of African sleeping sickness), and in ciliated... 

The proteins are synthesized in the cytoplasm and transferred to the mitochondria once they have been completely translated. The sequences tagged for the mitochondria have a presequence at the N terminus of the protein. This 15-35 amino acid signaling peptide, containing a large munber of positive side chains, is recognized by specific receptors that bring the proteins to the membrane surface of the mitochondrion. The... 

It is postulated that the inner membrane and its contents are derived from an ancient aerobic bacterium that invaded a primitive cell during the early stages of evolution and is an example of endosymbiosis. A relic from the past is that the mitochondrion has its own DMA (mtDNA) encoding 37 genes. Of these, 24 are needed for mtDNA translation and the rest encode proteins of the respiratory chain. Notably only 13 of the more than 85 proteins composing the mitochondrial respiratory chain are encoded in mtDNA. The others are encoded by the nuclear DNA and imported from the cytoplasm. 

Fig. 9. Hypothesis on the control of hemoglobin synthesis in chick embryo blastoderm by control of the synthesis of ALA-synthetase. In the nucleus a repressor protein (I) blocks transcription, and a 5jS-H steroid acts as a derepressor, permitting the structural gene (II) to code for the mRNA of ALA-synthetase. In the cytoplasm the information in the mRNA is translated into the enzyme ALA-synthetase (E,) which migrates into the mitochondrion where ALA (III) is made and finally converted by other enzymes (E2-E7) to heme (IV). Heme controls the synthesis of globin either by acting at the initiating site or by permitting proper folding of the globin.

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