, Volume 43, Issue 2, pp 135-147
Date: 25 Feb 2011

Electron transport chain dysfunction by H2O2 is linked to increased reactive oxygen species production and iron mobilization by lipoperoxidation: studies using Saccharomyces cerevisiae mitochondria

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The mitochondrial electron transport chain (ETC) contains thiol groups (−SH) which are reversibly oxidized to modulate ETC function during H2O2 overproduction. Since deleterious effects of H2O2 are not limited to –SH oxidation, due to the formation of other H2O2-derived species, some processes like lipoperoxidation could enhance the effects of H2O2 over ETC enzymes, disrupt their modulation by –SH oxidation and increase superoxide production. To verify this hypothesis, we tested the effects of H2O2 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 H2O2 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.