Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The key gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) is subjected to catabolite inactivation and degradation when glucose-starved cells are replenished with fresh glucose. In various studies, the proteasome and the vacuole have each been reported to be the major site of FBPase degradation. Because different growth conditions were used in these studies, we examined whether variations in growth conditions could alter the site of FBPase degradation. Here, we demonstrated that FBPase was degraded outside the vacuole (most likely in the proteasome), when glucose was added to cells that were grown in low glucose media for a short period of time. By contrast, cells that were grown in the same low glucose media for longer periods of time degraded FBPase in the vacuole in response to glucose. Another gluconeogenic enzyme malate dehydrogenase (MDH2) showed the same degradation characteristics as FBPase in that the short term starvation of cells led to a non-vacuolar degradation, whereas long term starvation resulted in the vacuolar degradation of this protein. The N-terminal proline is required for the degradation of FBPase and MDH2 for both the vacuolar and non-vacuolar proteolytic pathways. The cAMP signaling pathway and the phosphorylation of glucose were needed for the vacuolar-dependent degradation of FBPase and MDH2. By contrast, the cAMP-dependent signaling pathway was not involved in the non-vacuolar degradation of these proteins, although the phosphorylation of glucose was required.
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PMID:Degradation of the gluconeogenic enzymes fructose-1,6-bisphosphatase and malate dehydrogenase is mediated by distinct proteolytic pathways and signaling events. 1535 89

In Saccharomyces cerevisiae, glucose starvation induces key gluconeogenic enzymes such as fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2) and phosphoenolpyruvate carboxykinase, while glucose addition inactivates these enzymes. Significant progress has been made identifying mechanisms that mediate the "catabolite inactivation" of FBPase and MDH2. For example, the site of their degradation has been shown to change, depending on the duration of starvation. When glucose is added to short-termed starved cells, these proteins are degraded in the proteasome. However, when glucose is added to long-termed starved cells, they are degraded in the vacuole by a selective autophagy pathway. For the vacuole pathway, these proteins are first imported into novel vesicles called Vid (vacuole import and degradation) vesicles. Following import, Vid vesicles merge with the endocytic pathway. Future experiments will be directed at understanding the molecular mechanisms that regulate the switch from proteasomal to vacuolar degradation and determining the site of Vid vesicle biogenesis.
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PMID:A selective autophagy pathway that degrades gluconeogenic enzymes during catabolite inactivation. 1951 75

Upon starving Saccharomyces cerevisiae of glucose, the key gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2), isocitrate lyase (Icl1p) and phosphoenolpyruvate carboxykinase (Pck1p) are induced. When glucose is added to cells that have been starved for 3 days, these gluconeogenic enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. Moreover, it has been determined that during glucose starvation, these cargo proteins interact with the target of rapamycin complex 1 (TORC1), which is comprised of Tor1p, Tco89p, Lst8p and Kog1p. However, following glucose replenishment, Tor1p dissociates from the cargo proteins. We have determined that cells overexpressing TOR1 inhibited the phosphorylation of FBPase and its subsequent degradation in the vacuole. Interestingly, while the deletion of TCO89 inhibited FBPase degradation, it did not inhibit the phosphorylation of FBPase. Both Tor1p and Tco89p were found in endosomes originating from the plasma membrane as well as in retrograde vesicles forming from the vacuole membrane. Here we further discuss our findings and elaborate on our current model of the Vid pathway.
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PMID:The TOR complex 1 is required for the interaction of multiple cargo proteins selected for the vacuole import and degradation pathway. 2133 Dec 50

The ability to rapidly respond to nutrient changes is a fundamental requirement for cell survival. Here, we show that the zinc cluster regulator Znf1 responds to altered nutrient signals following glucose starvation through the direct control of genes involved in non-fermentative metabolism, including those belonged to the central pathways of gluconeogenesis (PCK1, FBP1 and MDH2), glyoxylate shunt (MLS1 and ICL1) and the tricarboxylic acid cycle (ACO1), which is demonstrated by Znf1-binding enrichment at these promoters during the glucose-ethanol shift. Additionally, reduced Pck1 and Fbp1 enzymatic activities correlate well with the data obtained from gene transcription analysis. Cells deleted for ZNF1 also display defective mitochondrial morphology with unclear structures of the inner membrane cristae when grown in ethanol, in agreement with the substantial reduction in the ATP content, suggesting for roles of Znf1 in maintaining mitochondrial morphology and function. Furthermore, Znf1 also plays a role in tolerance to pH and osmotic stress, especially during the oxidative metabolism. Taken together, our results clearly suggest that Znf1 is a critical transcriptional regulator for stress adaptation during non-fermentative growth with some partial overlapping targets with previously reported regulators in Saccharomyces cerevisiae.
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PMID:Zinc cluster protein Znf1, a novel transcription factor of non-fermentative metabolism in Saccharomyces cerevisiae. 2567 51