Distinct Intracellular Localization of Gpd1p and Gpd2p, the Two Yeast Isoforms of NAD+-dependent Glycerol-3-phosphate Dehydrogenase, Explains Their Different Contributions to Redox-driven Glycerol Production

Valadi, Åsa; Granath, Katarina; Gustafsson, Lena; Adler, Lennart

doi:10.1074/jbc.m403310200

Cited by 82 publications

(70 citation statements)

References 54 publications

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“…As in cells grown in glucose, a significant portion of the Gpd1p-GFP signal remained diffuse in the cytosol in oleic acid-incubated cells. This agrees with previously published reports of both cytosolic and peroxisomal localizations for Gpd1p (24,25) and suggests the existence of a mechanism regulating Gpd1p localization.…”

Section: Gpd1psupporting

confidence: 82%

“…Gpd1p is primarily peroxisomal upon exposure to oleic acid. It has been suggested that Gpd1p may be part of a glycerol 3-phosphate shuttle to regenerate NAD ϩ from NADH produced by ␤-oxidation (25). This mechanism of NAD ϩ regeneration could be an alternative to the malate/oxaloacetate cycle.…”

Section: Discussionmentioning

confidence: 99%

“…Gpd1p is generally considered a cytosolic protein, but quantitative mass spectrometry of the S. cerevisiae peroxisomal proteome and live cell fluorescence microscopy identified a pool of Gpd1p in peroxisomes (24,25). Peroxisomes play major roles in oxidative stress in both the generation of, and protection of cells from, reactive oxygen species (26).…”

mentioning

confidence: 99%

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Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Jung

Marelli

Rachubinski

et al. 2010

Journal of Biological Chemistry

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Gpd1p is a cytosolic NAD؉ -dependent glycerol 3-phosphate dehydrogenase that also localizes to peroxisomes and plays an essential role in the cellular response to osmotic stress and a role in redox balance. Here, we show that Gpd1p is directed to peroxisomes by virtue of an N-terminal type 2 peroxisomal targeting signal (PTS2) in a Pex7p-dependent manner. Significantly, localization of Gpd1p to peroxisomes is dependent on the metabolic status of cells and the phosphorylation of aminoacyl residues adjacent to the targeting signal. Exposure of cells to osmotic stress induces changes in the subcellular distribution of Gpd1p to the cytosol and nucleus. This behavior is similar to Pnc1p, which is coordinately expressed with Gpd1p, and under conditions of cell stress changes its subcellular distribution from peroxisomes to the nucleus where it mediates chromatin silencing. Although peroxisomes are necessary for the ␤-oxidation of fatty acids in yeast, the localization of Gpd1p to peroxisomes is not. Rather, shifts in the distribution of Gpd1p to different cellular compartments in response to changing cellular status suggests a role for Gpd1p in the spatial regulation of redox potential, a process critical to cell survival, especially under the complex stress conditions expected to occur in the wild.Glycerol 3-phosphate dehydrogenase (Gpd1p) is one of two NAD ϩ -dependent glycerol 3-phosphate dehydrogenases in yeast (1, 2). It is classically defined as a cytosolic enzyme that catalyzes the conversion of dihydroxyacetone phosphate (DHAP) 2 and NADH to glycerol 3-phosphate (Glycerol 3-phosphate) and NAD ϩ (2). In unstressed cells, this reaction prevents the accumulation of DHAP (3), which can otherwise be transformed into methyl glyoxylate (MG) (3, 4), a toxic compound that interacts with proteins (5-7). This reaction also allows for the reoxidation of NADH to NAD ϩ , which can serve as a buffer for cytosolic redox balance, compensating for cellular reactions that produce NADH (2). Moreover, glycerol 3-phosphate is a key metabolite for the synthesis of glyceride lipids and phospholipids, as well as for the formation of glycerol (8 -12).Under hyperosmotic stress, Saccharomyces cerevisiae, as well as other yeasts, accumulates glycerol as a major solute (13,14). This increased production of glycerol is caused mainly by an enhanced activity of Gpd1p, and accordingly, Gpd1p is essential for growth under osmotic stress (2, 15). In addition, GPD1 expression is altered by a wide variety of stresses, including heat, cold, and oxidative stress (16 -18), suggesting its regulation is controlled by stress. Genome-wide monitoring of transcript changes in yeast under various stress conditions also showed that GPD1 belongs to a large group of common stressresponse genes (19, 20); however, its regulation is complex and appears to be controlled by multiple signaling pathways (21). This likely reflects the multiple metabolic changes that yeast cells undergo in response to different stresses (19,22,23) and the function of Gpd1p at the int...

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Section: Gpd1psupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Jung

Marelli

Rachubinski

et al. 2010

Journal of Biological Chemistry

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“…2) under nonstress conditions results primarily from maintenance of the cytosolic redox balance (NADH), particularly under anaerobic conditions (12,20,292,356). The cellular NADH concentration is low, and continuous reoxidation is crucial to maintain glycolytic flux.…”

Section: Vol 72 2008 Metabolic Engineering Of Saccharomyces Cerevismentioning

confidence: 99%

Progress in Metabolic Engineering of Saccharomyces cerevisiae

Nevoigt

2008

Microbiol Mol Biol Rev

526

333

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SUMMARY The traditional use of the yeast Saccharomyces cerevisiae in alcoholic fermentation has, over time, resulted in substantial accumulated knowledge concerning genetics, physiology, and biochemistry as well as genetic engineering and fermentation technologies. S. cerevisiae has become a platform organism for developing metabolic engineering strategies, methods, and tools. The current review discusses the relevance of several engineering strategies, such as rational and inverse metabolic engineering, evolutionary engineering, and global transcription machinery engineering, in yeast strain improvement. It also summarizes existing tools for fine-tuning and regulating enzyme activities and thus metabolic pathways. Recent examples of yeast metabolic engineering for food, beverage, and industrial biotechnology (bioethanol and bulk and fine chemicals) follow. S. cerevisiae currently enjoys increasing popularity as a production organism in industrial (“white”) biotechnology due to its inherent tolerance of low pH values and high ethanol and inhibitor concentrations and its ability to grow anaerobically. Attention is paid to utilizing lignocellulosic biomass as a potential substrate.

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“…7A). However, Gpd1p and Pnc1p are also targeted to peroxisomes (28,53). So far, no peroxisomespecific function has been described for both enzymes, and we speculate that the peroxisomal import of both enzymes serves a stress-induced regulatory function.…”

Section: Discussionmentioning

confidence: 97%

Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae

Effelsberg

Cruz-Zaragoza

Tonillo

et al. 2015

Journal of Biological Chemistry

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Background: PTS2 proteins Gpd1p and Pnc1p are imported into peroxisomes in a PTS2 receptor-dependent manner. Results: PTS2co-receptor Pex21p is required for peroxisomal piggyback import of Gpd1p and Pnc1p. Conclusion: PTS2 co-receptors Pex18p and Pex21p enable targeting of distinct cargo proteins under variable stress conditions. Significance: The life span-regulating Pnc1p is transported into peroxisomes via a novel import route.

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Distinct Intracellular Localization of Gpd1p and Gpd2p, the Two Yeast Isoforms of NAD+-dependent Glycerol-3-phosphate Dehydrogenase, Explains Their Different Contributions to Redox-driven Glycerol Production

Cited by 82 publications

References 54 publications

Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Dynamic Changes in the Subcellular Distribution of Gpd1p in Response to Cell Stress

Progress in Metabolic Engineering of Saccharomyces cerevisiae

Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae

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