title: Electron transport chain dysfunction by H(2)O (2) is linked to increased reactive oxygen species production and iron mobilization by lipoperoxidation: studies using Saccharomyces cerevisiae mitochondria.
abstract: The mitochondrial electron transport chain (ETC) contains thiol groups (-SH) which are reversibly oxidized to modulate ETC function during H(2)O(2) overproduction. Since deleterious effects of H(2)O(2) are not limited to -SH oxidation, due to the formation of other H(2)O(2)-derived species, some processes like lipoperoxidation could enhance the effects of H(2)O(2) over ETC enzymes, disrupt their modulation by -SH oxidation and increase superoxide production. To verify this hypothesis, we tested the effects of H(2)O(2) on ETC activities, superoxide production and iron mobilization in mitochondria from lipoperoxidation-resistant native yeast and lipoperoxidation-sensitized yeast. Only complex III activity from lipoperoxidation-sensitive mitochondria exhibited a higher susceptibility to H(2)O(2) and increased superoxide production. The recovery of ETC activity by the thiol reductanct β-mercaptoethanol (BME) was also altered at complex III, and a role was attributed to lipoperoxidation, the latter being also responsible for iron release. A hypothetical model linking lipoperoxidation, increased complex III damage, superoxide production and iron release is given.
authors.affiliation: Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mich., México.
authors.forename: Christian
authors.initials: C
authors.lastname: Cortés-Rojo
authors.forename: Mirella
authors.initials: M
authors.lastname: Estrada-Villagómez
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Calderón-Cortés
authors.forename: Mónica
authors.initials: M
authors.lastname: Clemente-Guerrero
authors.forename: Ricardo
authors.initials: R
authors.lastname: Mejía-Zepeda
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.forename: Alfredo
authors.initials: A
authors.lastname: Saavedra-Molina
mesh_terms: D045222:Electron Transport Chain Complex Proteins; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D008954:Models, Biological; D016877:Oxidants / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D013481:Superoxides; D006861:Hydrogen Peroxide; D007501:Iron