Kinetic Regulation of the Mitochondrial Glycerol-3-phosphate Dehydrogenase by the External NADH Dehydrogenase in Saccharomyces cerevisiae

Påhlman, I.-L.; Larsson, Christer; Avéret, Nicole; Bunoust, Odile; Boubekeur, Samira; Gustafsson, Lena; Rigoulet, Michel

doi:10.1074/jbc.m204079200

Cited by 43 publications

(30 citation statements)

References 22 publications

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“…15 Alternatively, cytosolic NADH can be oxidized by the respiratory chain via the glycerol-3-phosphate shuttle, which consists of cytosolic NADH-linked glycerol-3-phosphate dehydrogenase and a membrane-bound glycerol-3-phosphate : ubiquinone oxido-reductase. 150 Furthermore, aerobic growth with D-and L-lactate as carbon source is also permitted via the inducible D,Llactate dehydrogenases localized on the external face of the inner mitochondrial membrane. 46 …”

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confidence: 99%

Role of the non‐respiratory pathways in the utilization of molecular oxygen by Saccharomyces cerevisiae

Rosenfeld

Beauvoit

2003

Yeast

132

110

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Saccharomyces cerevisiae is a facultative anaerobe devoid of mitochondrial alternative oxidase. In this yeast, the structure and biogenesis of the respiratory chain, on the one hand, and the functional interactions of oxidative phosphorylation with the cellular energetic metabolism, on the other, are well documented. However, to our knowledge, the molecular aspects and the physiological roles of the non-respiratory pathways that utilize molecular oxygen have not yet been reviewed. In this paper, we review the various non-respiratory pathways in a global context of utilization of molecular oxygen in S. cerevisiae. The roles of these pathways are examined as a function of environmental conditions, using either physiological, biochemical or molecular data. Special attention is paid to the characterization of the so-called 'cyanide-resistant respiration' that is induced by respiratory deficiency, catabolic repression and oxygen limitation during growth. Finally, several aspects of oxygen sensing are discussed.

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confidence: 99%

Role of the non‐respiratory pathways in the utilization of molecular oxygen by Saccharomyces cerevisiae

Rosenfeld

Beauvoit

2003

Yeast

132

110

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“…1). In addition, Gut2p has been demonstrated to work in a complex together with Nde1p/Nde2p and its activity seems to be strongly inhibited by the activity of these external NADH dehydrogenases [20,24]. This fact implicates that the catalytic role of Gut2p could be insufficient in promoting growth on glycerol under specific conditions, like those occurring during growth on synthetic medium, in which the synthesis of amino acids results in an excess of NADH production.…”

Section: Discussionmentioning

confidence: 92%

Generation of an evolved Saccharomyces cerevisiae strain with a high freeze tolerance and an improved ability to grow on glycerol

Merico

Ragni

Galafassi

et al. 2010

J Ind Microbiol Biotechnol

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Glycerol is a residue generated during biodiesel production and represents around 10% of the total product output. Biodiesel production is currently having a significant impact on glycerol price, leading to an increased interest in the use of glycerol as a cheap substrate for fermentation processes. We have analysed the growth kinetics of two wild-type strains of Saccharomyces cerevisiae grown on synthetic media containing glycerol as the sole carbon and energy source. Both strains were initially unable to grow when cultivated under these conditions, and an unusually long lag phase was necessary prior to the appearance of slow-growing cells. Following the application of an "evolutionary engineering" approach, we obtained S. cerevisiae strains with an improved ability to grow on glycerol. We report here the isolation of an evolved strain that exhibits a reduction of the lag phase, a threefold increase of the specific growth rate and a higher glycerol consumption rate compared to wild-type strains. The evolved strain has retained its fermentative activity, producing ethanol at the same rate and yield as the wild type. Interestingly, the yeast biomass obtained by cultivating the evolved strain on synthetic glycerol-based media also showed a high viability after prolonged storage at -20°C. The strategy adopted in our study could be easily applied to obtain S. cerevisiae strains with new industrially relevant traits, such as an improved ability to use cheap substrates and high resistance to freeze and thaw procedures.

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“…In addition, we have shown that the activation of NADH dehydrogenase inhibits the Gut2p in such a manner that, at a saturating concentration of NADH, glycerol 3-phosphate is not used as a respiratory substrate. This effect is not a consequence of a direct action of NADH on Gut2p activity because both NADH dehydrogenase and its substrate are needed for Gut2p inhibition (10).…”

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confidence: 99%

“…The Nde1p/Nde2p system, which is localized in the inner mitochondrial membrane with the catalytic sites projecting toward the intermembrane space, has been shown to directly oxidize cytosolic NADH (7,8). The glycerol 3-phosphate shuttle system, which involves the FADdependent Gut2p (10), is situated in the inner membrane of the mitochondria with the catalytic site projecting toward the cytosol and has been shown to be active in maintaining a cytosolic redox balance (9). In this system, the co-factor NADH is oxidized to NAD ϩ by the cytosolic glycerol-3-phosphate dehydrogenase (Gpd1p) when catalyzing the reduction of dihydroxyacetone phosphate (DHAP) 1 to glycerol 3-phosphate.…”

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confidence: 99%

Competition of Electrons to Enter the Respiratory Chain

Bunoust

Devin

Avéret

et al. 2005

Journal of Biological Chemistry

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In the yeast Saccharomyces cerevisiae, the most important systems for conveying excess cytosolic NADH to the mitochondrial respiratory chain are the external NADH dehydrogenases (Nde1p and Nde2p) and the glycerol-3-phosphate dehydrogenase shuttle. In the latter system, NADH is oxidized to NAD ؉ and dihydroxyacetone phosphate is reduced to glycerol 3-phosphate by the cytosolic Gpd1p. Subsequently, glycerol 3-phosphate donates electrons to the respiratory chain via mitochondrial glycerol-3-phosphate dehydrogenase (Gut2p). At saturating concentrations of NADH, the activation of external NADH dehydrogenases completely inhibits glycerol 3-phosphate oxidation. Studies on the functionally isolated enzymes demonstrated that neither Nde1p nor Nde2p directly inhibits Gut2p. Thus, the inhibition of glycerol 3-phosphate oxidation may be caused by competition for the entrance of electrons into the respiratory chain. Using single deletion mutants of Nde1p or Nde2p, we have shown that glycerol 3-phosphate oxidation via Gut2p is inhibited fully when NADH is oxidized via Nde1p, whereas only 50% of glycerol 3-phosphate oxidation is inhibited when Nde2p is functioning. By comparing respiratory rates with different respiratory substrates, we show that electrons from Nde1p are favored over electrons coming from Ndip (internal NADH dehydrogenase) and that when electrons come from either Nde1p or Nde2p and succinodehydrogenase, their use by the respiratory chain is shared to a comparable extent. This suggests a very specific competition for electron entrance into the respiratory chain, which may be caused by the supramolecular organization of the respiratory chain. The physiological consequences of such regulation are discussed.The yeast Saccharomyces cerevisiae lacks transhydrogenase activity (1, 2), and the redox couple NAD ϩ /NADH cannot pass through the mitochondrial membrane. Hence, systems for NADH turnover in mitochondria as well as in the cytosol are required under both aerobic and anaerobic conditions. The reason for this is that several processes result in production of NADH, i.e. several processes are, contrary to ethanol fermentation, not redox neutral. The synthesis of 1 mol of glycerol, the second major by-product of S. cerevisiae cells fermenting glucose, results in the consumption of 1 mol of NADH, whereas other by-products such as acetate lead to the production of cytosolic NADH. The largest part of excess cytosolic NADH formation is connected to biomass production (3, 4). The synthesis of proteins and nucleic acids and even the highly reduced lipids is associated with assimilatory NADH production. In particular, NADH is generated in the biosynthetic pathways of amino acid synthesis (3, 4). Anaerobically, the only means by which S. cerevisiae can reoxidize surplus production of NADH is by glycerol production (2, 5). Aerobically, several systems exist for conveying excess cytosolic NADH to the mitochondrial electron transport chain in S. cerevisiae (6). The two most important systems in this respect seem to be the exte...

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Kinetic Regulation of the Mitochondrial Glycerol-3-phosphate Dehydrogenase by the External NADH Dehydrogenase in Saccharomyces cerevisiae

Cited by 43 publications

References 22 publications

Role of the non‐respiratory pathways in the utilization of molecular oxygen by Saccharomyces cerevisiae

Role of the non‐respiratory pathways in the utilization of molecular oxygen by Saccharomyces cerevisiae

Generation of an evolved Saccharomyces cerevisiae strain with a high freeze tolerance and an improved ability to grow on glycerol

Competition of Electrons to Enter the Respiratory Chain

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