mtDNA replication Sample Clauses

mtDNA replication. The presence of DNA in mitochondria was first reported in 1963 when Xxxxxx and Xxxxxx Xxxx were studying chick embryo mitochondria under the electron microscope. They observed fibres within the mitochondria which contained DNA-like characteristics and proposed that mitochondria contained their own DNA, separate from the nuclear counterpart (Nass and Nass, 1963). A year later, in 1964, mtDNA was purified from xxxxx’x yeast (Xxxxxx et al., 1964) and in 1966, a study reported the differentiation of nuclear and mitochondrial protein systems due to a differing susceptibility to antibiotic treatment (Xxxxx-Xxxxxx and Xxxxxxx, 1966). A timeline of the main discoveries related to mtDNA in yeast is depicted in Figure 1.6. The mitochondrial genome copy number in an organism is highly variable and regulated in a cell-specific manner (Xxxxxxxx et al., 2014). It is estimated that there are thousands of mitochondria in most mammalian somatic cells, each containing 1 to 10 copies of mtDNA, and mammalian oocytes contain at least 100,000 copies of mtDNA per cell (Shoubridge and Wai, 2007). The mitochondrial genome, which in mammals is 16.6kb, encodes 13 polypeptides, all of which are components of the complexes of the mitochondrial respiratory chain. The energetic levels of the cell are therefore dependent on the presence of an adequate mtDNA copy number, which is sufficient to maintain the metabolic requirements of the cell. The mtDNA replication machinery is nuclear encoded. The mitochondrial DNA polymerase (pol γ) has a catalytic and accessory subunit, termed pol γ-α and pol γ-β respectively, which are responsible for the synthesis of the new mtDNA strand. The mtDNA is unwound in the 5’ to 3’ direction by the mtDNA helicase, which in mammals is known as Twinkle. mtDNA single stranded binding protein (SSBP) consequently acts to stabilize the single strand, thereby preventing rewinding of the strands (Figure 1.7).