The integrity of the mitochondrial inner membrane is essential for efficient ATP production in mitochondria. In this study, we analyze the effect of heavy metal ions Cd²⁺ and Cu²⁺ at low concentrations on the mitochondrial inner membrane permeability and test the hypothesis that the mechanism of action of Cd²⁺ and Cu²⁺ ions is different due to the ability of the latter to undergo redox-cycling and consequently to stimulate the production of reactive oxygen specines (ROS) and to induce lipid peroxidation. We show that 5 nmol Cu²⁺ per mg of protein but not 5 nmol Cd²⁺ per mg of protein increase membrane ion permeability in the whole range of the physiologically relevant membrane potential (Δψ) values, especially at high Δψ. Moreover, Cu²⁺ ions at this concentration enhance the formation of H₂O₂ in the mitochondrial matrix by 43% and induce lipid peroxidation as indicated by an increase in the amount of thiobarbituric acid reactive substances (TBARS) by 26%. Meanwhile, Cd2+ ions at the same concentration have no significant effect on H₂O₂ formation or lipid peroxidation. Only a higher amount of Cd²⁺ions significantly stimulates the formation of H₂O₂. However, this is not accompanied by an increase in lipid peroxidation, which suggests that, in contrast to Cu²⁺-induced ROS production, the mechanism of Cd²⁺-induced ROS production most likely does not involve formation of the hydroxyl radical. In conclusion, we show that Cu²⁺ but not Cd²⁺ ions at a low concentration stimulate ROS production and induce accumulation of TBARS, suggesting that, indeed, Cu²⁺ions increase membrane ion permeability by stimulating lipid peroxidation.

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2011 - Vol.57
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