Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 9, Issue -, Pages -Publisher
WILEY
DOI: 10.1038/msb.2013.21
Keywords
autophagy; mass spectrometry; metabolism; nutrient starvation; Saccharomyces cerevisiae
Categories
Funding
- NSF [MCB-0643859, CBET-0941143]
- Joint DOE-AFOSR Award [DOE DE-SC0002077-AFOSR FA9550-09-1-0580]
- NIH [CA163591, RO1 GM076562]
- Princeton University Center for Quantitative Biology [P50 GM071508]
- Government of Canada through Genome Canada
- Ontario Genomics Institute [2009-OGI-ABC-1405]
- Ontario Research Fund [ORF-GL2-01-004]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [0941143] Funding Source: National Science Foundation
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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.
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