- One of the distinctive features of mitochondria is that they have their own DNA. When compared to nuclear DNA, it is known that mitochondrial DNA (mtDNA) not only has a much higher rate of spontaneous mutation, but also arises from metabolically distinct precursor pools. Others from our laboratory have demonstrated that abnormalities in DNA precursor pools (dNTPs) can be mutagenic, and that mitochondrial dNTP pools can be highly asymmetric with respect to their genomes. However, at present, neither the metabolic source of mitochondrial dNTPs nor the mechanisms of their regulation have been identified.
In all cells, ribonucleotide reductases (RNRs) are the enzymes that synthesize the four deoxyribonucleotides required for DNA synthesis. Through their role in the biosynthesis of deoxyribonucleoside triphosphates (dNTPs), RNRs play a crucial role in the regulation of their accumulation. At present, the existence of a mitochondrial RNR (mtRNR) in the mitochondrial matrix is intensely debated.
In this study, we show that mitochondria in a variety of tissues contain RNR activity. We compared mtRNR activity to cytoslic RNR activity in the presence of inhibitors and found that the activities were different. Given that mtRNR activity was several-fold higher than cytosolic RNR activity, it was unlikely that the mitochondrial activity was the
result of a cytosolic contamination. Although unfinished at present, we have also made progress in attempts to isolate the putative mtRNR gene. Thus, our present results suggest that there is indeed a form of ribonucleotide reductase associated with the mammalian mitochondrion that is enzymatically distinct from the major cytosolic form of this enzyme.