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)

A purification and some properties of proteinase A from yeast are described. A specific macromolecular inhibitor of proteinase A from yeast cytosol has been isolated and shown to be a protein (molecular weight 7,700) consisting of a majority of polar amino acids. Proline, arginine, cysteine and tryptophan were not detected in the inhibitor. Possible biological functions of proteinase A and the proteinase A-inhibitor (and of other yeast proteinases and their inhibitors) in the following processes are discussed: general protein turnover, catabolite inactivation of enzymes, enzyme degradation at starvation and at transition to spore formation, and activation of pre-enzymes and precursor proteins by limited proteolysis.
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PMID:Characteristics and functions of proteinase A and its inhibitors in yeast. 2 96

For determination of the physiological role and mechanism of vacuolar proteolysis in the yeast Saccharomyces cerevisiae, mutant cells lacking proteinase A, B, and carboxypeptidase Y were transferred from a nutrient medium to a synthetic medium devoid of various nutrients and morphological changes of their vacuoles were investigated. After incubation for 1 h in nutrient-deficient media, a few spherical bodies appeared in the vacuoles and moved actively by Brownian movement. These bodies gradually increased in number and after 3 h they filled the vacuoles almost completely. During their accumulation, the volume of the vacuolar compartment also increased. Electron microscopic examination showed that these bodies were surrounded by a unit membrane which appeared thinner than any other intracellular membrane. The contents of the bodies were morphologically indistinguishable from the cytosol; these bodies contained cytoplasmic ribosomes, RER, mitochondria, lipid granules and glycogen granules, and the density of the cytoplasmic ribosomes in the bodies was almost the same as that of ribosomes in the cytosol. The diameter of the bodies ranged from 400 to 900 nm. Vacuoles that had accumulated these bodies were prepared by a modification of the method of Ohsumi and Anraku (Ohsumi, Y., and Y. Anraku. 1981. J. Biol. Chem. 256:2079-2082). The isolated vacuoles contained ribosomes and showed latent activity of the cytosolic enzyme glucose-6-phosphate dehydrogenase. These results suggest that these bodies sequestered the cytosol in the vacuoles. We named these spherical bodies "autophagic bodies." Accumulation of autophagic bodies in the vacuoles was induced not only by nitrogen starvation, but also by depletion of nutrients such as carbon and single amino acids that caused cessation of the cell cycle. Genetic analysis revealed that the accumulation of autophagic bodies in the vacuoles was the result of lack of the PRB1 product proteinase B, and disruption of the PRB1 gene confirmed this result. In the presence of PMSF, wild-type cells accumulated autophagic bodies in the vacuoles under nutrient-deficient conditions in the same manner as did multiple protease-deficient mutants or cells with a disrupted PRB1 gene. As the autophagic bodies disappeared rapidly after removal of PMSF from cultures of normal cells, they must be an intermediate in the normal autophagic process. This is the first report that nutrient-deficient conditions induce extensive autophagic degradation of cytosolic components in the vacuoles of yeast cells.
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PMID:Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. 140 May 75

Glutamine synthetase activity is modulated by nitrogen repression and by two distinct inactivation processes. Addition of glutamine to exponentially grown yeast leads to enzyme inactivation. 50% of glutamine synthetase activity is lost after 30 min (a quarter of the generation time). Removing glutamine from the growth medium results in a rapid recovery of enzyme activity. A regulatory mutation (gdhCR mutation) suppresses this inactivation by glutamine in addition to its derepressing effect on enzymes involved in nitrogen catabolism. The gdhCR mutation also increases the level of proteinase B in exponentially grown yeast. Inactivation of glutamine synthetase is also observed during nitrogen starvation. This inactivation is irreversible and consists very probably of a proteolytic degradation. Indeed, strains bearing proteinase A, B and C mutations are no longer inactivated under nitrogen starvation.
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PMID:Regulation of glutamine synthetase from Saccharomyces cerevisiae by repression, inactivation and proteolysis. 612 75

We have isolated a gene from Neurospora crassa that appears to encode a pepstatin-sensitive protease found both in membranes and in soluble contents of vacuoles. The gene contains two introns and encodes a 396-residue protein with a molecular mass of 42,900 Da. Because of the similarity of the protein to proteinase A in Saccharomyces cerevisiae the gene has been named pep-4. Strains with mutations in the pep-4 gene were generated in vivo by the gene RIPing procedure described by Selker and Garrett (Selker, E. U., and Garrett, P. W. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 6870-6874). The mutant strains were deficient in pepstatin-sensitive protease activity and did not appear to produce a major 42-kDa polypeptide in the vacuole. The mutant strains grew at the same rate as the wild type and had no other observable phenotype. When compared with inactivation of the PEP4 gene of S. cerevisiae, inactivation of the pep-4 gene in N. crassa produced a phenotype that was different in several ways. In N. crassa the mutant strains did not exhibit reduced sporulation or reduced viability after nitrogen starvation, and they had elevated levels of proteinase B and carboxypeptidase activities. The pep-4 gene appears to encode the N. crassa, homolog of proteinase A, but the maturation of vacuolar hydrolases appeared to be less dependent on this protease than has been observed in S. cerevisiae.
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PMID:Characterization of a vacuolar protease in Neurospora crassa and the use of gene RIPing to generate protease-deficient strains. 870 99

Acidification inside vacuoles has been shown to play a key role in a number of physiologically important cellular events. We studied the role of vacuolar membrane H(+)-ATPase in the autophagic process of Saccharomyces cerevisiae. Mutants lacking VMA genes which encode their subunits of the vacuolar H(+)-ATPase accumulated autophagic bodies in vacuoles on starvation. vma mutants also had a defect in protein degradation induced by starvation. In vma mutants, the activities of vacuolar proteases were remarkably lower than those of the wild-type. Overexpression of vacuolar proteases did not overcome the defect in the disintegration of autophagic bodies in vma mutant, even the overexpressed proteinase A and proteinase B being substantially localized to the vacuolar compartment and undergoing proper proteolytic maturation. Our results showed that the acidification of vacuoles is not required for the formation and delivery of autophagosomes to vacuoles, but is essential for the disintegration of autophagic bodies.
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PMID:Acidification of vacuoles is required for autophagic degradation in the yeast, Saccharomyces cerevisiae. 908 9

Aminopeptidase I (API) is delivered to the yeast vacuole by one of two alternative pathways, cytoplasm to vacuole targeting (Cvt) or autophagy, depending on nutrient conditions. Genetic, morphological, and biochemical studies indicate that the two pathways share many of the same molecular components. The Cvt pathway functions during vegetative growth, while autophagy is induced during starvation. Both pathways involve the formation of cytosolic vesicles that fuse with the vacuole. In either case, the mechanism of vesicle formation is not known. Autophagic uptake displays a greater capacity for cytosolic protein sequestration. This suggests the involvement of an inducible protein(s) that allows the vesicle-forming machinery to adapt to the increased degradative needs of the cell. We have analyzed the biosynthesis of Aut7p, a protein required for both pathways. We find Aut7p expression is induced by nitrogen starvation. Aut7p is degraded by a process dependent on both proteinase A and Cvt/autophagy components. Protease accessibility assays demonstrate that Aut7p is located within vesicles in strains defective in vesicle delivery or breakdown. Finally, the aut7/cvt5 mutant accumulates precursor API at a stage prior to vesicle completion. These data suggest that Aut7p is induced during autophagy and delivered to the vacuole together with precursor API by Cvt/autophagic vesicles.
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PMID:The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. 1068 75

Selective disintegration of membrane-enclosed autophagic bodies is a feature of eukaryotic cells not studied in detail. Using a Saccharomyces cerevisiae mutant defective in autophagic-body breakdown, we identified and characterized Aut5p, a glycosylated integral membrane protein. Site-directed mutagenesis demonstrated the relevance of its putative lipase active-site motif for autophagic-body breakdown. aut5Delta cells show reduced protein turnover during starvation and are defective in maturation of proaminopeptidase I. Most recently, by means of the latter phenotype, Aut5p was independently identified as Cvt17p. In this study we additionally checked for effects on vacuolar acidification and detected mature vacuolar proteases, both of which are prerequisites for autophagic-body lysis. Furthermore, biologically active hemagglutinin-tagged Aut5p (Aut5-Ha) localizes to the endoplasmic reticulum (nuclear envelope) and is targeted to the vacuolar lumen independent of autophagy. In pep4Delta cells immunogold electron microscopy located Aut5-Ha at approximately 50-nm-diameter intravacuolar vesicles. Characteristic missorting in vps class E and fab1Delta cells, which affects the multivesicular body (MVB) pathway, suggests vacuolar targeting of Aut5-Ha similar to that of the MVB pathway. In agreement with localization of Aut5-Ha at intravacuolar vesicles in pep4Delta cells and the lack of vacuolar Aut5-Ha in wild-type cells, our pulse-chase experiments clearly indicated that Aut5-Ha degradation with 50 to 70 min of half-life is dependent on vacuolar proteinase A.
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PMID:Aut5/Cvt17p, a putative lipase essential for disintegration of autophagic bodies inside the vacuole. 1156 94