Induction of a menadione-dependent respiratory shunt by a platinum complex

The causes of cancer revisited: “Mitochondrial malignancy” and ROS-induced oncogenic transformation – Why mitochondria are targets for cancer therapy

“…One-electron reduction of VK3 leads to the formation of VK3-semiquinone that in the presence of oxygen is oxidized back to VK3 while oxygen is in turn, one-electron reduced to generate Å O À 2 that causes oxidative stress and cytotoxicity. Thus, many of the early biochemical studies showed that VK3 acts as an artificial electron carrier/shunt like ubiquinone (UbQ, CoQ) in the mitochondrial respiratory chain, capable of restoring function when either of complexes I, II or III is inhibited (Slater, 1959;Kolesova et al, 1978;Brivet-Chevillotte and di Rago, 1989;Korneev et al, 1990). VK3 was also used clinically in early attempts to overcome debilitating genetic mutational deficiencies in the respiratory chain complexes of patients suffering from associated mitochondrial disease (reviewed in Mowat et al, 1999;Argov et al, 1986), although bypassing the blockages by administering electron acceptors has not proven very successful.…”