DNA mtDNA

Mitochondria have their own DNA (mtDNA) and genetic continuity. This DNA only encodes 13 peptide subunits synthesized in the matrix that are components of complexes I, III, IV, and V of the respiratory chain. Most mitochondrial proteins are synthesized on cytoplasmic ribosomes and imported by specific mechanisms to their specific locations in the mitochondrion (see below). 

Mitochondria are unique organelles in man and higher animals in that they contain their own genome. Mitochondrial DNA (mtDNA) in humans is a small (16.5 kb), circular genome that encodes only 13 proteins, 22 transfer RNA (tRNA), and 2 ribosomal RNA (rRNA) molecules. mtDNA is inherited only from the mother and is present in multiple copies within one mitochondrion. 

Mitochondria are unique organelles in that they contain their own DNA (mtDNA), which, in addition to ribosomal RN A (rRNA) and transfer RN A (tRNA)-coding sequences, also encodes 13 polypeptides which are components of complexes I, III, IV, and V (Anderson et al., 1981). This fact has important implications for both the genetics and the etiology of the respiratory chain disorders. Since mtDNA is maternally-inherited, a defect of a respiratory complex due to a mtDNA deletion would be expected to show a pattern of maternal transmission. However the situation is complicated by the fact that the majority of the polypeptide subunits of complexes I, III, IV, and V, and all subunits of complex II, are encoded by nuclear DNA. A defect in a nuclear-coded subunit of one of the respiratory complexes would be expected to show classic Mendelian inheritance. A further complication exists in that it is now established that some respiratory chain disorders result from defects of communication between nuclear and mitochondrial genomes (Zeviani et al., 1989). Since many mitochondrial proteins are synthesized in the cytosol and require a sophisticated system of posttranslational processing for transport and assembly, it is apparent that a diversity of genetic errors is to be expected. 

The third human DNA SRM developed by NIST was designed to meet the need for quality control when amplifying and sequencing human mitochondrial DNA (mtDNA). 

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. 

While DNA is more robust than often depicted in movies, age and extreme conditions such as a fire can substantially degrade it. In such cases, mitochondrial DNA (mtDNA) is best used. Unlike nuclear DNA, mitochondrial genome exists in thousands of copies, is less apt to degrade, and is inherited only from the mother. Here, STRs are not analyzed, but rather the focus is on variable regions of the mitochondrial genome. Such analyses take much longer but are used for situations where time is not essential. 

Mitochondria contain the only extranuclear genomic DNA (mtDNA) and it encodes 13 proteins using a genetic code different from that in the nucleus. These proteins are key components of OXPHOS I, III, IV and V, but not complex II, which is solely encoded by nuclear DNA (nuDNA). Inhibition of mtDNA transcription as well as expression of mitochondrial proteins will therefore lead to loss of OXPHOS function. Probably the best known drugs that inhibit mtDNA synthesis are the nucleotide... 

Nucleoside analogues are drugs used to treat HIV and hepatitis. One such drug fialuridine and other drugs of this type have caused severe hepatic dysfunction. This dysfunction was characterized by fatty liver and fatal liver failure. Fialuridine caused fatal damage in 5 of 12 patients in early clinical trials. Fialuridine inhibits DNA polymerases. However, there is also DNA in the mitochondria [mitochondrial DNA (mtDNA)]. 

Eukaryotic cells also have organelles, mitochondria (Fig. 24-6) and chloroplasts, that contain DNA. Mitochondrial DNA (mtDNA) molecules are much smaller than the nuclear chromosomes. In animal cells, mtDNA contains fewer than 20,000 bp (16,569 bp in human mtDNA) and is a circular duplex. Each mitochondrion typically has two to ten copies of this mtDNA molecule, and the number can rise to hundreds in certain cells when an embryo is undergoing cell differentiation. In a few organisms (trypanosomes, for example) each mitochondrion contains thousands of copies of mtDNA, organized into a complex and interlinked matrix known as a kinetoplast. Plant cell mtDNA ranges in size from... 

FIGURE 24-6 A dividing mitochondrion. Some mitochondrial proteins and RNAs are encoded by one of the copies of the mitochondrial DNA (none of which are visible here). The DNA (mtDNA) is replicated each time the mitochondrion divides, before cell division. 

Of the very few variations in the genetic code that we know of, most occur in mitochondrial DNA (mtDNA), which encodes only 10 to 20 proteins. Mitochondria have their own tRNAs, so their code variations do not affect the much larger cellular genome. 

Each mitochondrion contains several molecules of DNA (mtDNA), usually in a closed, circular form, as well as the ribosomes, tRNA molecules, and enzymes needed for protein synthesis.1 23 26 With rare exceptions almost all of the mitochondrial DNA in a human cell is inherited from the mother.6 263 The size of the DNA circles varies from 16-19 kb in animals27 to over 200 kb in many higher plants. Complete sequences of many mitochondrial DNAs are known.28 283 Among these are the 16,569 bp human mtDNA,29 the 16,338 bp bovine mtDNA, the 16,896 bp mtDNA of the wallaroo Macropus robustus,30 and the 17,533 bp mtDNA of the amphibian Xenopus laevis.31 32 The sea urchin Paracentotus lividus has a smaller 15,697 bp genome. However, the order of the genes in this and other invertebrate mtDNA is different from that in mammalian mitochondria.33 Protozoal mtDNAs vary in size from 5900 bp for the... 

H. citelli, H. diminuta and H. microstoma, one of which is mitochondrial DNA (mtDNA) (394). The mtDNA of H. diminuta has been isolated (118) and has been shown to be a typical circular molecule. The characteristics of H. diminuta DNA are shown in Table 6.11. In contrast, E. multilocularis and E. granulosus produced two distinct DNA bands after fractionation in caesium chloride, but there was no evidence that the DNA from either band represented mtDNA (493). There is presumably so little mtDNA in comparison to nuclear DNA in these organisms that it is completely masked in preparations of total DNA by this method. That this is the case has been shown by a recent study (976), where a different procedure, based on the selective precipitation of nucleic acids by cetyltrimethylammonium bromide (CTAB), was employed to extract mtDNA from isolated mitochondria. Some 300 g and 50 g, respectively, of Taenia spp. and Echinococcus sp. tissue yielded approximately only 1 ng mtDNA. 

Human mitochondrial DNA (mtDNA), a circular supercoiled DNA of about 16,469 base pairs, codes for 13 proteins, 22 tRNAs, and 2 ribosomal RNAs (rRNAs) using a code slightly different from the virtually universal code (page... 

Mitochondrial DNA (mtDNA), which is clonally inherited through maternal lineages, has proved to be a powerful genetic marker for phyloge-... 

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