A glycolytic metabolon in Saccharomyces cerevisiae is stabilized by F-actin
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In the Saccharomyces cerevisiae glycolytic pathway, 11 enzymes catalyze the stepwise conversion of glucose to two molecules of ethanol plus two CO 2 molecules. In the highly crowded cytoplasm, this pathway would be very inefficient if it were dependent on substrate/enzyme diffusion. Therefore, the existence of a multi-enzymatic glycolytic complex has been suggested. This complex probably uses the cytoskeleton to stabilize the interaction of the various enzymes. Here, the role of filamentous actin (F-actin) in stabilization of a putative glycolytic metabolon is reported. Experiments were performed in isolated enzyme/actin mixtures, cytoplasmic extracts and permeabilized yeast cells. Polymerization of actin was promoted using phalloidin or inhibited using cytochalasin D or latrunculin. The polymeric filamentous F-actin, but not the monomeric globular G-actin, stabilized both the interaction of isolated glycolytic pathway enzyme mixtures and the whole fermentation pathway, leading to higher fermentation activity. The associated complexes were resistant against inhibition as a result of viscosity (promoted by the disaccharide trehalose) or inactivation (using specific enzyme antibodies). In S. cerevisiae, a glycolytic metabolon appear to assemble in association with F-actin. In this complex, fermentation activity is enhanced and enzymes are partially protected against inhibition by trehalose or by antibodies. Structured digital abstract ALD physically interacts with PGK and GAPDH by anti bait coimmunoprecipitation (View interaction) ALD physically interacts with GAPDH and PGK by affinity chromatography technology (View interaction) In Saccharomyces cerevisiae a multi-enzymatic glycolytic complex (a glycolytic metabolon) would increase efficiency. F-actin stabilized a glycolytic complex. Actin oligomers (phalloidin) but not actin monomers (cytochalasin D or latrunculin) stabilized a glycolytic metabolon with high fermentation activity and resistance to viscosity or enzyme antibody-mediated inhibition. © 2013 FEBS.
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actin; cytoskeleton; enzyme association; glycolytic metabolon; yeast metabolism cytochalasin D; enzyme antibody; F actin; fructose bisphosphate aldolase; G actin; glyceraldehyde 3 phosphate dehydrogenase; glycolytic enzyme; latrunculin B; multienzyme complex; phalloidin; phosphoglycerate kinase; trehalose; actin; cytochalasin D; fungus antibody; fused heterocyclic rings; multienzyme complex; phalloidin; Saccharomyces cerevisiae protein; thiazolidine derivative; trehalose; tubulin modulator; article; catalysis; cell membrane permeability; complex formation; controlled study; enzyme activity; enzyme inhibition; enzyme isolation; enzyme stability; fermentation; molecular interaction; nonhuman; prediction; priority journal; protein assembly; protein function; protein polymerization; protein protein interaction; Saccharomyces cerevisiae; yeast cell; actin filament; chemistry; comparative study; cytoplasm; cytoskeleton; drug antagonism; drug effect; drug potentiation; enzyme complex formation; enzyme stability; enzymology; glycolysis; glycolytic metabolon; kinetics; metabolism; metabolome; polymerization; Saccharomyces cerevisiae; viscosity; yeast; Saccharomyces cerevisiae; actin; cytoskeleton; enzyme association; glycolytic metabolon; yeast metabolism; Actin Cytoskeleton; Actins; Antibodies, Fungal; Bicyclo Compounds, Heterocyclic; Cytochalasin D; Cytoplasm; Enzyme Stability; Fermentation; Glycolysis; Kinetics; Metabolome; Multienzyme Complexes; Phalloidine; Polymerization; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Thiazolidines; Trehalose; Tubulin Modulators; Viscosity
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