Mechanistic role of ergosterol in membrane rigidity and cycloheximide resistance in Saccharomyces cerevisiae

Biochimica Et Biophysica Acta
Fumiyoshi Abe, Toshiki Hiraki

Abstract

Mutants of Saccharomyces cerevisiae defective in the late steps of ergosterol biosynthesis are viable but accumulate structurally altered sterols within the plasma membrane. Despite the significance of pleiotropic abnormalities in the erg mutants, little is known about how sterol alterations mechanically affect the membrane structure and correlate with individual mutant phenotypes. Here we demonstrate that the membrane order and occurrence of voids are determinants of membrane rigidity and hypersensitivity to a drug. Among five ergDelta mutants, the erg2Delta mutant exhibited the most marked sensitivity to cycloheximide. Notably, measurement of time-resolved anisotropy indicated that the erg2Delta mutation decreased the membrane order parameter (S), and dramatically increased the rotational diffusion coefficient (D(w)) of 1-[4-(trimethylamino)pheny]-6-phenyl-1,3,5-hexatriene (TMA-DPH) in the plasma membrane by 8-fold, providing evidence for the requirement of ergosterol for membrane integrity. The IC(50) of cycloheximide was closely correlated with S/D(w) in these strains, suggesting that the membrane disorder and increasing occurrence of voids within the plasma membrane synergistically enhance passive diffusion of cycloheximid...Continue Reading

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Citations

Apr 28, 2010·Applied Microbiology and Biotechnology·Thi Minh Ngoc TaYves Waché
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