Nucleotide degradation and ribose salvage in yeast
Abstract 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 asso...
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| Format: | Article |
| Language: | English |
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Springer Nature
2013-05-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2013.21 |
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| _version_ | 1849388704863354880 |
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| author | Yi‐Fan Xu Fabien Létisse Farnaz Absalan Wenyun Lu Ekaterina Kuznetsova Greg Brown Amy A Caudy Alexander F Yakunin James R Broach Joshua D Rabinowitz |
| author_facet | Yi‐Fan Xu Fabien Létisse Farnaz Absalan Wenyun Lu Ekaterina Kuznetsova Greg Brown Amy A Caudy Alexander F Yakunin James R Broach Joshua D Rabinowitz |
| author_sort | Yi‐Fan Xu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-3604c67e8fc44eb89cba3406fe3e0b45 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2013-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-3604c67e8fc44eb89cba3406fe3e0b452025-08-20T03:42:11ZengSpringer NatureMolecular Systems Biology1744-42922013-05-019111210.1038/msb.2013.21Nucleotide degradation and ribose salvage in yeastYi‐Fan Xu0Fabien Létisse1Farnaz Absalan2Wenyun Lu3Ekaterina Kuznetsova4Greg Brown5Amy A Caudy6Alexander F Yakunin7James R Broach8Joshua D Rabinowitz9Lewis Sigler Institute for Integrative Genomics, Princeton UniversityUniversité de Toulouse, INSA, UPS, INP; LISBPDepartment of Molecular Biology, Princeton UniversityLewis Sigler Institute for Integrative Genomics, Princeton UniversityDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of TorontoDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of TorontoDonnelly Centre for Cellular and Biomolecular Research, University of TorontoDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of TorontoDepartment of Molecular Biology, Princeton UniversityLewis Sigler Institute for Integrative Genomics, Princeton UniversityAbstract 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.https://doi.org/10.1038/msb.2013.21autophagymass spectrometrymetabolismnutrient starvationSaccharomyces cerevisiae |
| spellingShingle | Yi‐Fan Xu Fabien Létisse Farnaz Absalan Wenyun Lu Ekaterina Kuznetsova Greg Brown Amy A Caudy Alexander F Yakunin James R Broach Joshua D Rabinowitz Nucleotide degradation and ribose salvage in yeast Molecular Systems Biology autophagy mass spectrometry metabolism nutrient starvation Saccharomyces cerevisiae |
| title | Nucleotide degradation and ribose salvage in yeast |
| title_full | Nucleotide degradation and ribose salvage in yeast |
| title_fullStr | Nucleotide degradation and ribose salvage in yeast |
| title_full_unstemmed | Nucleotide degradation and ribose salvage in yeast |
| title_short | Nucleotide degradation and ribose salvage in yeast |
| title_sort | nucleotide degradation and ribose salvage in yeast |
| topic | autophagy mass spectrometry metabolism nutrient starvation Saccharomyces cerevisiae |
| url | https://doi.org/10.1038/msb.2013.21 |
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