title: Reactive oxygen species production induced by ethanol in Saccharomyces cerevisiae increases because of a dysfunctional mitochondrial iron-sulfur cluster assembly system.
abstract: Ethanol accumulation during fermentation contributes to the toxic effects in Saccharomyces cerevisiae, impairing its viability and fermentative capabilities. The iron-sulfur (Fe-S) cluster biogenesis is encoded by the ISC genes. Reactive oxygen species (ROS) generation is associated with iron release from Fe-S-containing enzymes. We evaluated ethanol toxicity, ROS generation, antioxidant response and mitochondrial integrity in S. cerevisiae ISC mutants. These mutants showed an impaired tolerance to ethanol. ROS generation increased substantially when ethanol accumulated at toxic concentrations under the fermentation process. At the cellular and mitochondrial levels, ROS were increased in yeast treated with ethanol and increased to a higher level in the ssq1∆, isa1∆, iba57∆ and grx5∆ mutants - hydrogen peroxide and superoxide were the main molecules detected. Additionally, ethanol treatment decreased GSH/GSSG ratio and increased catalase activity in the ISC mutants. Examination of cytochrome c integrity indicated that mitochondrial apoptosis was triggered following ethanol treatment. The findings indicate that the mechanism of ethanol toxicity occurs via ROS generation dependent on ISC assembly system functionality. In addition, mutations in the ISC genes in S. cerevisiae contribute to the increase in ROS concentration at the mitochondrial and cellular level, leading to depletion of the antioxidant responses and finally to mitochondrial apoptosis.
authors.affiliation: Lab de Biotecnología Microbiana, Instituto de Investigaciones Químico-Biológicas, Morelia, Michoacán, México.
authors.forename: Rocio V
authors.initials: RV
authors.lastname: Pérez-Gallardo
authors.forename: Luis S
authors.initials: LS
authors.lastname: Briones
authors.forename: Alma L
authors.initials: AL
authors.lastname: Díaz-Pérez
authors.forename: Sergio
authors.initials: S
authors.lastname: Gutiérrez
authors.forename: José S
authors.initials: JS
authors.lastname: Rodríguez-Zavala
authors.forename: Jesús
authors.initials: J
authors.lastname: Campos-García
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity; D005285:Fermentation; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D000431:Ethanol; D013455:Sulfur; D007501:Iron; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: Fe-S biogenesis; Saccharomyces cerevisiae; ethanol toxicity; iron-sulfur cluster (ISC); reactive oxygen species (ROS)