Down-regulation of fatty acid synthase increases the resistance of Saccharomyces cerevisiae cells to H2O2.
Changes in plasma membrane permeability caused by H2O2 were recently found to be involved in the adaptation to H2O2, but the mechanism responsible for this change remains largely unknown. Here this mechanism was addressed and two lines of evidence showed for the first time that fatty acid synthase (Fas) plays a key role during the cellular response of Saccharomyces cerevisiae to H2O2: (1) adaptation was associated with a decrease in both Fas expression and activity; (2) more importantly, decreasing Fas activity by 50% through deletion of one of the FAS alleles increased the resistance to lethal doses of H2O2. The mechanism by which a decrease of Fas expression causes a higher resistance to H2O2 was not fully elucidated. However, the fas1Delta strain plasma membrane had large increases in the levels of lignoceric acid (C24:0) (40%) and cerotic acid (C26:0) (50%), suggesting that alterations in the plasma membrane composition are involved. Very-long-chain fatty acids (VLCFA) through interdigitation or by modulating formation of lipid rafts may decrease the overall or localized plasma membrane permeability to H2O2, respectively, thus conferring a higher resistance to H2O2.
Matias
Ana C
AC
Centro de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, 1749-016 Lisboa, Portugal.
Pedroso
Nuno
N
Teodoro
Nuno
N
Marinho
H Susana
HS
Antunes
Fernando
F
Nogueira
José Manuel
JM
Herrero
Enrique
E
Cyrne
Luísa
L
D002462:Cell Membrane / Q000737:chemistry; D015536:Down-Regulation; D025141:Drug Resistance, Fungal / Q000235:genetics; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; C017364:hexacosanoic acid; D064429:Fatty Acid Synthases; C526685:FAS1 protein, S cerevisiae; C010210:lignoceric acid