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Yeast POS5 NADH Kinase: Effects of a Mitochondrial Mutator Mutation on Mitochondrial Nucleotides

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  • Saccharomyces cerevisiae contains three NAD⁺/NADH kinases, one of which is localized in mitochondria and phosphorylates NADH in preference to NAD⁺. Strand et al (Euk. Cell 2:809 (2003)) reported that a yeast mutation in POS5, which encodes the mitochondrial NADH kinase, is a mutator, specific for mitochondrial genes. Because of the involvement of NADPH in deoxyribonucleotide biosynthesis, we asked whether mitochondria in a pos5 deletion mutant contain abnormal deoxyribonucleoside triphosphate pools. We found pools of the four dNTPs² to be more than doubled in mutant mitochondrial extracts relative to wild-type. This might partly explain the mitochondrial mutator phenotype. However, the loss of antioxidant protection is also likely to be significant. To this end, we measured pyridine nucleotide pools in mutant and wild-type mitochondrial extracts and found levels of NADPH to be diminished about fourfold in Δpos5 mitochondrial extracts, with NADP⁺ diminished to a lesser degree. Our data suggest that both dNTP abnormalities and lack of antioxidant protection contribute to elevated mitochondrial gene mutagenesis in cells lacking the mitochondrial NADH kinase. The data also confirm previous reports of the specific function of POS5p in mitochondrial NADP⁺ and NADPH biosynthesis.
  • Keywords: NADH kinase, Deoxyribonucleoside triphosphates, Mitochondria, Mutator, Pyridine nucleotides
  • Keywords: NADH kinase, Deoxyribonucleoside triphosphates, Mitochondria, Mutator, Pyridine nucleotides
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  • Wheeler, L. J., & Mathews, C. K. (2012). Effects of a mitochondrial mutator mutation in yeast POS5 NADH kinase on mitochondrial nucleotides. The Journal of Biological Chemistry, 287(37), 31218-31222. doi: 10.1074/jbc.M112.394031
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  • 287
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  • 37
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  • This work was supported in [whole or in part,] by National Institutes of Health Grant R01 GM073744 and by Army Research Office Grant 55953-LS.
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