Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae

Al-Saryi, N. A., Al-Hejjaj, M. Y., Van Roermund, C. W. T. , Hulmes, G. E., Ekal, L., Payton, C., Wanders, R. J. A. and Hettema, E. H. (2017) Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae. Scientific Reports, 7 (1). ISSN 2045-2322

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In Saccharomyces cerevisiae, peroxisomes are the sole site of fatty acid β-oxidation. During this process, NAD+ is reduced to NADH. When cells are grown on oleate medium, peroxisomal NADH is reoxidised to NAD+ by malate dehydrogenase (Mdh3p) and reduction equivalents are transferred to the cytosol by the malate/oxaloacetate shuttle. The ultimate step in lysine biosynthesis, the NAD+-dependent dehydrogenation of saccharopine to lysine, is another NAD+-dependent reaction performed inside peroxisomes. We have found that in glucose grown cells, both the malate/oxaloacetate shuttle and a glycerol-3-phosphate dehydrogenase 1(Gpd1p)-dependent shuttle are able to maintain the intraperoxisomal redox balance. Single mutants in MDH3 or GPD1 grow on lysine-deficient medium, but an mdh3/gpd1� double mutant accumulates saccharopine and displays lysine bradytrophy. Lysine biosynthesis is restored when saccharopine dehydrogenase is mislocalised to the cytosol in mdh3/gpd1� cells. We conclude that the availability of intraperoxisomal NAD+ required for saccharopine dehydrogenase activity can be sustained by both shuttles. The extent to which each of these shuttles contributes to the intraperoxisomal redox balance may depend on the growth medium. We propose that the presence of multiple peroxisomal redox shuttles allows eukaryotic cells to maintain the peroxisomal redox status under different metabolic conditions. © 2017 The Author(s).

Keywords:Redox chemistry
Subjects:C Biological Sciences > C130 Cell Biology
Divisions:College of Science > School of Life Sciences
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ID Code:29175
Deposited On:26 Nov 2017 18:00

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