Ribosomes mitochondrial

Certain antibiotics (for example, chloramphenicol) inhibit mitochondrial protein synthesis, but not cytoplasmic protein synthesis, because mitochondrial ribosomes are similar to prokaryotic ribosomes. 

In many ways, mitochondria resemble bacteria for example, the mitochondrial ribosomal RNA genes of all eukaryotes have been traced back to the eubacteria [10]. This can explain why some antibacterial compounds with the target of inhibiting bacterial protein synthesis also inhibit mitochondrial protein synthesis [6, 11, 12], resulting in hematotoxicity. Tetracycline, chloramphemcol and some oxazolidinone antibiotics have been shown to induce hematotoxicity by inhibiting mitochondrial protein synthesis [13]. 

Mitochondrial ribosomes of human cells are structurally similar to those of prokaryotes. 

DNA-sequence of mitochondrial ribosomal RNA genes. Proceedings of the National Academy of Sciences, USA 92 2017-2020. 

Matrix of the mitochondrion This gel-like solution in the interior of mitochondria is fifty percent protein. These molecules include the enzymes responsible for the oxidation of pyruvate, amino acids, fatty acids (by p-oxidation), and those of the tricarboxylic acid (TCA) cycle. The synthesis of urea and heme occur partially in the matrix of mitochondria. In addition, the matrix contains NAD+and FAD (the oxidized forms of the two coenzymes that are required as hydrogen acceptors) and ADP and Pj, which are used to produce ATP. [Note The matrix also contains mitochondrial RNA and DNA (mtRNA and mtDNA) and mitochondrial ribosomes.]... 

In addition to bacterialike mitochondrial ribosomes and small circular molecules of DNA, mitochondria may contain variable numbers of dense granules of calcium phosphate, either Ca3(P04)2 or hydroxylapa-tite (Fig. 8-34),4/18 as well as of phospholipoprotein.4... 

Why does mtDNA contain any protein genes, or why does mtDNA even exist It seems remarkable that the cells of our bodies make the 100 or so extra proteins (encoded in the nucleus) needed for replication, transcription, amino acid activation, and mitochondrial ribosome formation and bring these into the mitochondria for the sole purpose of permitting the synthesis there of 13 proteins. The explanation is not evident. What are the 13 proteins ... 

Mitochondrial ribosomal genes are much smaller than even their bacterial homologues. Expansion segments found in nuclear ortho-logues are, of course, absent. Gerbi (1996) referred to contraction segments as features found in the bacterium E. coli that are absent from other rRNAs, particularly mt rRNAs. The... 

The drug binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction. Because of the similarity of mammalian mitochondrial ribosomes to those of bacteria, protein synthesis in these organelles may be inhibited at high circulating chloramphenicol levels, producing bone marrow toxicity. 

Correct choice = B. At high concentrations, tetracycline enters mammalian cells by diffusion and interacts with mitochondrial ribosomes, blocking access of the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site. Severe photosensitive dermatitis occurs when the patient receiving tetracycline is exposed to sun or ultraviolet rays. 

Matrix. This large internal space contains a highly concentrated mixture of hundreds of enzymes, including those required for the oxidation of pyruvate and fatty acids for the citric acid cycle. The matrix also contains several identical copies of the mitochondrial DNA genome, special mitochondrial ribosomes, tRNAs, and various enzymes required for expression of mitochondrial genes. 

Hibbett DS, Donoghue MJ Progress toward a phylogenetic classification of the Polyporaceae through parsimony analyses of mitochondrial ribosomal DNA sequences. Can J Bot 1995 73(suppl 1) s853-s861. 

Erythromycin (a macrolide Group I inhibitor ineffective in the archaea) impairs the functioning of bacterial SOS subunits by interacting with the central loop of domain IV of the 23S rRNA (Fig. 6). In bacteria ( . coli), erythromycin resistance is conferred by an A to U base change, or by the dimethylation of the A residue [142]. In erythromycin-resistant yeast S. cerevisiae) mitochondria, the equivalent A residue is replaced by a G[141]. In accord with these observations, all of the archaeal 23 S rRNAs sequenced until now resemble the large subunit rRNA of eucarya and of the erythromycin-resistant yeast mitochondrial ribosomes in having a G instead of the critical A residue [150]. Since the remaining structure of the peptidyltransferase loop is conserved in all of the... 

Fig. 12.5. Biogenesis and assembly of cytochrome 6-c, complex in the inner mitochondrial membrane. Cytochrome fc-Cj complex contains at least five different subunits COREI (corl), COREII (corll), nonheme iron protein (Fe-S), cytochrome c, (cyt Cj), and cytochrome b (cyt b). Cytochrome f> is a mitochondrial gene product and is probably assembled into the inner membrane (IM) via vectorial translation by mitochondrial ribosomes. The other subunits are synthesized on cytoplasmic ribosomes as larger precursors. The precursors, perhaps in association with a cytoplasmic factor , are attached to receptors on the mitochondrial outer membrane (OM). The complex laterally diffuses to the junctions of the outer and inner membranes, and with the help of a hypothetical translocator the precursors are imported across the membrane. Pre-Corl, pre-Corll, and the pre-nonheme iron protein cross the two membranes, whereas cytochrome c, becomes anchored to the outer face of the inner membrane, facing the intermembrane space (IMS). Cytochrome b is assembled inside the inner membrane, and the nonheme iron protein and Corl and Corll are assembled into the matrix side of the inner membrane. The N-terminal extensions are removed by a soluble matrix protease. The N-terminal extension of cytochrome c, is removed in two steps the first is catalyzed by the matrix protease and the second probably by a protease located on the outer face of the inner membrane.

Mitochondrial ribosomes are comprised of a large subunit, 16S rRNA and a small subunit 12S rRNA. 

Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu W-Q, Armos KS, Cortopassi GA, Jaber L, Rotter JI, Shohat M, Eischel-Ghodsian N (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 4 289-294. 

Fischel-Ghodsian N, Prezant TR, Bn X, Oztas S. Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity. Am J Otolaryngol 1993 14(6) 399 03. 

The complementary nature of MALDI-MS and ESI-MS-MS can also be exploited to increase the proteome coverage via PSA [36]. A fraction (20%) of the column effluent of a nano-LC column was sent to ESI-MS-MS, while the rest was fractionated onto MALDI spots for automated off-line LC-MALDI-MS and MS-MS analysis. About 63% overlap in protein identified from a digest of mammalian mitochondrial ribosomes was observed, but unique proteins were also identified by either technique. 

D. Treatment of bacterial infections Antibiotics that selectively affect bacterial function and have minimal side effects in humans are usually selected to treat bacterial infections. Rifampicin, which inhibits the initiation of prokaryotic RNA synthesis, is used to treat tuberculosis. Streptomycin, tetracycline, chloramphenicol, and erythromycin inhibit protein synthesis on prokaiyotic ribosomes and are used for many infections. Chloramphenicol affects mitochondrial ribosomes and must be used with caution. 

C. These antibiotics inhibit protein synthesis in prokaryotes thus, they can be used to treat bacterial infections. One of their undesirable side effects, however, is that they also inhibit protein synthesis on mitochondrial ribosomes (which are of the 70S prokaryotic class). 

Some antibiotics are active against both bacterial and mammalian cells. One example is chloramphenicol, which inhibits peptidyltransferase in both bacterial and mitochondrial ribosomes, although eukaryotic cytoplasmic ribosomes are unaffected. Such a drug may be clinically useful if a concentration range can be maintained in the patient in which the antibacterial action is substantial but toxic effects on host cells are minimal. However, because of the potential for toxicity, such antibiotics are used only in serious infections when other drugs fail. 

Chloramphenicol Inhibits peptydyltransferase of mitochondrial ribosomes. Is inactive against cytoplasmic ribosomes. 

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