The plasma membrane-enriched fraction proteome response during adaptation to hydrogen peroxide in Saccharomyces cerevisiae

Abstract

In Saccharomyces cerevisiae, adaptation to hydrogen peroxide (H2O2) decreases plasma membrane permeability to H2O2, changes its lipid composition and reorganizes ergosterol-rich microdomains by a still unknown mechanism. Here we show, by a quantitative analysis of the H2O2-induced adaptation effect on the S. cerevisiae plasma membrane-enriched fraction proteome, using two-dimensional gel electrophoresis, that 44 proteins are differentially expressed. Most of these proteins were regulated at a post-transcriptional level. Fourteen of these proteins contain redox-sensitive cysteine residues and nine proteins are associated with lipid and vesicle traffic. In particular, three proteins found in eisosomes and in the eisosome-associated membrane compartment occupied by Can1p were up-regulated (Pil1p, Rfs1p and Pst2p) during adaptation to H2O2. Survival studies after exposure to lethal H2O2 doses using yeast strains bearing a gene deletion corresponding to proteins associated to lipid and vesicle traffic demonstrated for the first time that down-regulation of Kes1p, Vps4p and Ynl010wp and up-regulation of Atp1 and Atp2 increases resistance to H2O2. Moreover, for the pil1Δ strain, H2O2 at low levels produces a hormetic effect by increasing proliferation. In conclusion, these data further confirms the plasma membrane as an active cellular site during adaptation to H2O2 and shows that proteins involved in lipid and vesicle traffic are important mediators of H2O2 adaptation.