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

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.