Enzyme kinetics of the mitochondrial deoxyribonucleoside salvage pathway are not sufficient to support rapid mtDNA replication.

ABSTRACT: Using a computational model, we simulated mitochondrial deoxynucleotide metabolism and mitochondrial DNA replication. Our results indicate that the output from the mitochondrial salvage enzymes alone is inadequate to support a mitochondrial DNA replication duration of as long as 10 hours. We find that an external source of deoxyribonucleoside diphosphates or triphosphates (dNTPs), in addition to those supplied by mitochondrial salvage, is essential for the replication of mitochondrial DNA to complete in the experimentally observed duration of approximately 1 to 2 hours. For meeting a relatively fast replication target of 2 hours, almost two-thirds of the dNTP requirements had to be externally supplied as either deoxyribonucleoside di- or triphosphates, at about equal rates for all four dNT

SUBMITTER: Gandhi VV 

PROVIDER: S-EPMC3150320 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature