Modulation of plasma membrane lipid profile and microdomains by H2O2 in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, the rate of hydrogen peroxide (H(2)O(2)) diffusion through the plasma membrane decreases during adaptation to H(2)O(2) by a still unknown mechanism. Here, adaptation to H(2)O(2) was observed to modulate rapidly the expression of genes coding for enzymes involved in ergosterol and lipid metabolism. Adaptation to H(2)O(2) also alters plasma membrane lipid composition. The main changes were the following: (a) there was a decrease in oleic acid (30%) and in the ratio between unsaturated and saturated long-chain fatty acids; (b) the phosphatidylcholine:phosphatidylethanolamine ratio increased threefold; (c) sterol levels were unaltered but there was an increased heterogeneity of sterol-rich microdomains and increased ordered domains; (d) the levels of the sterol precursor squalene increased twofold, in agreement with ERG1 gene down-regulation; and (e) C26:0 became the major very long chain fatty acid owing to an 80% decrease in 2-hydroxy-C26:0 levels and a 50% decrease in C20:0 levels, probably related to the down-regulation of fatty acid elongation (FAS1, FEN1, SUR4) and ceramide synthase (LIP1, LAC1) genes. Therefore, H(2)O(2) leads to a reorganization of the plasma membrane microdomains, which may explain the lower permeability to H(2)O(2), and emerges as an important regulator of lipid metabolism and plasma membrane lipid composition.
Pedroso
Nuno
N
Centro de QuImica e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.
Matias
Ana C
AC
Cyrne
Luísa
L
Antunes
Fernando
F
Borges
Carlos
C
Malhó
Rui
R
de Almeida
Rodrigo F M
RF
Herrero
Enrique
E
Marinho
H Susana
HS
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000382:microbiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D000072237:ERG1 Potassium Channel; D004875:Ergosterol / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D021962:Membrane Microdomains / Q000187:drug effects* / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000032:analysis; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010713:Phosphatidylcholines / Q000032:analysis; D010714:Phosphatidylethanolamines / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013185:Squalene / Q000032:analysis; D013261:Sterols / Q000032:analysis
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C499639:Lip1 protein, S cerevisiae; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D019301:Oleic Acid; C483858:phosphatidylethanolamine; D013185:Squalene; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C513563:LAC1 protein, S cerevisiae; D000123:Acetyltransferases; C107118:ELO2 protein, S cerevisiae; C107119:SUR4 protein, S cerevisiae; D064429:Fatty Acid Synthases; C526685:FAS1 protein, S cerevisiae; D004875:Ergosterol