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Mitochondrial DNA Replication and Regulation

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Mitochondrial DNA (mtDNA) is crucial for cellular energy production, replicated by DNA polymerase gamma. Its replication is tightly controlled during embryogenesis to reduce mutation transmission. Human mtDNA contains 37 genes, with transcription varying by tissue, reflecting energy needs. The heart has the highest mitochondrial gene expression, influenced by factors like ACTH.

Mitochondrial DNA Replication and Its Enzymatic Machinery

Mitochondrial DNA (mtDNA) plays a pivotal role in cellular energy production, being replicated by a dedicated enzyme complex known as DNA polymerase gamma. This complex is composed of a catalytic subunit of 140 kDa, encoded by the POLG gene, and a pair of 55 kDa accessory subunits, encoded by the POLG2 gene. These components assemble into the replisome, which also includes TWINKLE helicase and mitochondrial single-stranded DNA-binding proteins (SSB). TWINKLE helicase unwinds the DNA in a 5' to 3' direction, facilitating replication. It is important to note that the genes encoding these proteins are found in the nuclear DNA, not within the mitochondrial genome itself.
Detailed model of mitochondrion with salmon pink outer membrane, dark pink inner cristae, blue DNA and gray ribosomes on a neutral background.

Regulation of Mitochondrial DNA Replication During Embryogenesis

The replication of mtDNA is stringently regulated during embryogenesis. There is a marked suppression of mtDNA replication from the stage of the fertilized oocyte to the preimplantation embryo. This decrease in mtDNA copy number is part of a phenomenon known as the mitochondrial bottleneck, which serves to minimize the transmission of deleterious mutations to offspring. The resumption of mtDNA replication is initiated in the trophectoderm cells of the blastocyst, whereas the inner cell mass cells postpone mtDNA replication until they differentiate into specific cell lineages, in response to developmental cues.

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00

The catalytic subunit of the enzyme complex is encoded by the ______ gene and has a molecular weight of ______.

POLG

140 kDa

01

The accessory subunits of the enzyme complex, each weighing ______, are encoded by the ______ gene.

55 kDa

POLG2

02

______ helicase assists in DNA unwinding during replication by moving in a ______ direction.

TWINKLE

5' to 3'

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