title: The sensitivity of yeast mutants to oleic acid implicates the peroxisome and other processes in membrane function.
abstract: The peroxisome, sole site of beta-oxidation in Saccharomyces cerevisiae, is known to be required for optimal growth in the presence of fatty acid. Screening of the haploid yeast deletion collection identified approximately 130 genes, 23 encoding peroxisomal proteins, necessary for normal growth on oleic acid. Oleate slightly enhances growth of wild-type yeast and inhibits growth of all strains identified by the screen. Nonperoxisomal processes, among them chromatin modification by H2AZ, Pol II mediator function, and cell-wall-associated activities, also prevent oleate toxicity. The most oleate-inhibited strains lack Sap190, a putative adaptor for the PP2A-type protein phosphatase Sit4 (which is also required for normal growth on oleate) and Ilm1, a protein of unknown function. Palmitoleate, the other main unsaturated fatty acid of Saccharomyces, fails to inhibit growth of the sap190delta, sit4delta, and ilm1delta strains. Data that suggest that oleate inhibition of the growth of a peroxisomal mutant is due to an increase in plasma membrane porosity are presented. We propose that yeast deficient in peroxisomal and other functions are sensitive to oleate perhaps because of an inability to effectively control the fatty acid composition of membrane phospholipids.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lockshon
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Surface
authors.forename: Emily O
authors.initials: EO
authors.lastname: Kerr
authors.forename: Matt
authors.initials: M
authors.lastname: Kaeberlein
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D010084:Oxidation-Reduction; D000074401:Peroxins; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005229:Fatty Acids, Monounsaturated; D006657:Histones; C493530:Htz1 protein, S cerevisiae; D008565:Membrane Proteins; C070895:PEX3 protein, S cerevisiae; C076587:PEX4 protein, S cerevisiae; D000074401:Peroxins; D029701:Saccharomyces cerevisiae Proteins; C008757:palmitoleic acid; D019301:Oleic Acid; D004257:DNA Polymerase II; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C511586:PEX1 protein, S cerevisiae