Nucleotide degradation and ribose salvage in yeast

• Published in: Molecular systems biology Vol. 9; no. 1; pp. 665 - n/a
• Main Authors: Xu, Yi‐Fan, Létisse, Fabien, Absalan, Farnaz, Lu, Wenyun, Kuznetsova, Ekaterina, Brown, Greg, Caudy, Amy A, Yakunin, Alexander F, Broach, James R, Rabinowitz, Joshua D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2013; John Wiley & Sons, Ltd; EMBO Press; Wiley; European Molecular Biology Organization; Springer Nature
• Subjects: Ablation; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Antioxidants; autophagy; BASIC BIOLOGICAL SCIENCES; Biochemistry; Biochemistry & Molecular Biology; Biodegradation; Carbon; Chromatography; Consumption; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Degradation; Depletion; E coli; EMBO21; EMBO36; Enzymes; Experiments; Gene deletion; Gene Expression Regulation, Fungal; Genetics; Genomes; Glyceraldehyde; Glyceraldehyde 3-Phosphate - metabolism; Grants; Hydrolase; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Kinases; Life Sciences; mass spectrometry; Metabolism; Metabolites; Metabolomics; N-Glycosyl Hydrolases - deficiency; N-Glycosyl Hydrolases - genetics; NADP; NADP - metabolism; Nitrogen; Nucleosides; Nucleotides; Nucleotides - metabolism; nutrient starvation; Nutrients; Oxidative stress; Pentose; Pentose phosphate pathway; Pentose Phosphate Pathway - genetics; Phosphatase; Phosphorylase; Phosphorylases; Physiology; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proteins; Purine-Nucleoside Phosphorylase - deficiency; Purine-Nucleoside Phosphorylase - genetics; Ribose; Ribose - metabolism; Ribosomes; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Software; Starvation; Stress, Physiological - genetics; Substrates; Sugar Phosphates; Transaldolase; Transaldolase - genetics; Transaldolase - metabolism; Yeast; Germany; nutrient starvation; mass spectrometry; metabolism; autophagy; Subject Categories: RNA; Saccharomyces cerevisiae; cellular metabolism Keywords: autophagy
• ISSN: 1744-4292; 1744-4292
• DOI: 10.1038/msb.2013.21

Nucleotide degradation is a universal metabolic capability. Here we combine metabolomics, genetics and biochemistry to characterize the yeast pathway. Nutrient starvation, via PKA, AMPK/SNF1, and TOR, triggers autophagic breakdown of ribosomes into nucleotides. A protein not previously associated with nucleotide degradation, Phm8, converts nucleotide monophosphates into nucleosides. Downstream steps, which involve the purine nucleoside phosphorylase, Pnp1, and pyrimidine nucleoside hydrolase, Urh1, funnel ribose into the nonoxidative pentose phosphate pathway. During carbon starvation, the ribose‐derived carbon accumulates as sedoheptulose‐7‐phosphate, whose consumption by transaldolase is impaired due to depletion of transaldolase's other substrate, glyceraldehyde‐3‐phosphate. Oxidative stress increases glyceraldehyde‐3‐phosphate, resulting in rapid consumption of sedoheptulose‐7‐phosphate to make NADPH for antioxidant defense. Ablation of Phm8 or double deletion of Pnp1 and Urh1 prevent effective nucleotide salvage, resulting in metabolite depletion and impaired survival of starving yeast. Thus, ribose salvage provides means of surviving nutrient starvation and oxidative stress. Metabolomics, genetics and biochemistry were combined to obtain the first complete map of the nucleotide degradation and ribose salvage pathway in yeast. This pathway promotes yeast survival in starvation and oxidative stress. Synopsis Metabolomics, genetics and biochemistry were combined to obtain the first complete map of the nucleotide degradation and ribose salvage pathway in yeast. This pathway promotes yeast survival in starvation and oxidative stress. During carbon starvation, ribose salvage from nucleotides promotes yeast survival. The salvage pathway requires the previously misannotated nucleotidase Phm8. Ribose‐derived carbon accumulates as sedoheptulose‐7‐phosphate. This carbon reserve enables rapid NADPH production in oxidative stress.