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Ribonucleotide Reductase Association with Mammalian Liver Mitochondria

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  • Deoxyribonucleoside triphosphate pools in mammalian mitochondria are highly asymmetric, and this asymmetry probably contributes toward the elevated mutation rate for the mitochondrial genome as compared with the nuclear genome. To understand this asymmetry, we must identify pathways for synthesis and accumulation of dNTPs within mitochondria. We have identified ribonucleotide reductase activity specifically associated with mammalian tissue mitochondria. Examination of immunoprecipitated proteins by mass spectrometry revealed R1, the large RNR subunit, in purified mitochondria. Significant enzymatic and immunological activity was seen in rat liver mitochondrial nucleoids, isolated as described by Wang, Y., and Bogenhagen, D. F. (2006) J. Biol. Chem. 281, 25791–25802. Moreover, incubation of respiring rat liver mitochondria with [¹⁴C]cytidine diphosphate leads to acccumulation of radiolabeled deoxycytidine and thymidine nucleotides within the mitochondria. Comparable results were seen with [¹⁴C]guanosine diphosphate. Ribonucleotide reduction within the mitochondrion, as well as outside the organelle, needs to be considered as a possibly significant contributor to mitochondrial dNTP pools.
  • This research was originally published in the Journal of Biological Chemistry. Chimploy, K., Song, S., Wheeler, L. J., & Mathews, C. K. Ribonucleotide reductase association with mammalian liver mitochondria. 2013. 288(18), 13145-13155. © the American Society for Biochemistry and Molecular Biology. This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Society for Biochemistry and Molecular Biology and can be found at: http://www.jbc.org/.
  • Keywords: deoxyribonucleotide metabolism, ribonucleotide reductase, mitochondria, nucleotide pool asymmetry
  • Keywords: deoxyribonucleotide metabolism, ribonucleotide reductase, mitochondria, nucleotide pool asymmetry
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  • Chimploy, K., Song, S., Wheeler, L. J., & Mathews, C. K. (2013). Ribonucleotide reductase association with mammalian liver mitochondria. The Journal of Biological Chemistry, 288(18), 13145-13155. doi:10.1074/jbc.M113.461111
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  • 288
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  • 18
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  • This work was supported in part by National Institutes of Health Grant R01 GM073744. This work was also supported by Army Research Office Grant 55953-LS. The proteomic analysis was carried out in the OSU Environmental Health Sciences Center mass spectrometry facility supported by NIEHS Center Grant ES000210.
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