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Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase.

Publication ,  Journal Article
Shianna, KV; Marchuk, DA; Strand, MK
Published in: Mitochondrion.
April 1, 2006

Disruption of the Saccharomyces cerevisiae mitochondrial NADH kinase POS5 increases the mitochondrial mutation rate 50-fold. Whereas most multicellular eukaryotic genomes have one NADH kinase gene, the yeast genome contains three distinct genes encoding NAD/H kinase activity. To determine if all three genes are essential for viability we constructed combinations of gene knockouts. We show that only the pos5Deltautr1Delta combination is synthetically lethal, demonstrating an essential overlapping function, and showing that NAD/H kinase activity is essential for eukaryotic viability. The single human NAD/H kinase gene can rescue the lethality of the double knockout in yeast, demonstrating that the single human gene can fill the various functions provided by the three yeast genes. The human NAD/H kinase gene harbors very common sequence variants, but all of these equally complement the synthetic lethality in yeast, illustrating that each of these are functionally wild-type. To understand the molecular mechanism of the mitochondrial genome instability of pos5 mutation we performed gene expression analysis on the pos5Delta. The pos5Delta resulted in an increase in expression of most of the iron transport genes including key genes involved in iron-sulfur cluster assembly. Decreased expression occurred in many genes involved in the electron transport chain. We show that the pos5Delta expression pattern is similar to the frataxin homolog knockout (yfh1Delta), the yeast model for Friedreich's ataxia. These combined data show that the POS5 NAD/H kinase is an important protein required for a variety of essential cellular pathways and that deficient iron-sulfur cluster assembly may play a critical role in the mitochondrial mutator phenotype observed in the pos5Delta.

Duke Scholars

Published In

Mitochondrion.

ISSN

1567-7249

Publication Date

April 1, 2006

Volume

6

Issue

2

Start / End Page

94 / 101

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 0604 Genetics
 

Citation

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MLA
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Shianna, K. V., Marchuk, D. A., & Strand, M. K. (2006). Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase. Mitochondrion., 6(2), 94–101.
Shianna, K. V., D. A. Marchuk, and M. K. Strand. “Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase.Mitochondrion. 6, no. 2 (April 1, 2006): 94–101.
Shianna KV, Marchuk DA, Strand MK. Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase. Mitochondrion. 2006 Apr 1;6(2):94–101.
Shianna, K. V., et al. “Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase.Mitochondrion., vol. 6, no. 2, Apr. 2006, pp. 94–101.
Shianna KV, Marchuk DA, Strand MK. Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase. Mitochondrion. 2006 Apr 1;6(2):94–101.
Journal cover image

Published In

Mitochondrion.

ISSN

1567-7249

Publication Date

April 1, 2006

Volume

6

Issue

2

Start / End Page

94 / 101

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 0604 Genetics