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Cadmium inhibits the electron transfer chain and induces reactive oxygen species.
Wang Y; Fang J; Leonard SS; Rao KMK
Free Radic Biol Med 2004 Jun; 36(11):1434-1443
Recent research indicates that cadmium (Cd) induces oxidative damage in cells; however, the mechanism of the oxidative stress induced by this metal is unclear. We investigated the effects of Cd on the individual complexes of the electron transfer chain (ETC) and on the stimulation of reactive oxygen species (ROS) production in mitochondria. The activity of complexes II (succinate:ubiquinone oxidoreductase) and III (ubiquinol:cytochrome c oxidoreductase) of mitochondrial ETC from liver, brain, and heart showed greater inhibition by Cd than the other complexes. Cd stimulated ROS production in the mitochondria of all three tissues mentioned above. The effect of various electron donors (NADH, succinate, and 2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinol) on ROS production was tested separately in the presence and in the absence of Cd. ESR showed that complex III might be the only site of ROS production induced by Cd. The results of kinetic studies and electron turnover experiments suggest that Cd may bind between semiubiquinone and cytochrome b566 of the Q0 site of cytochrome b of complex III, resulting in accumulation of semiubiquinones at the Q0 site. The semiubiquinones, being unstable, are prone to transfer one electron to molecular oxygen to form superoxide, providing a possible mechanism for Cd-induced generation of ROS in mitochondria.
Cadmium compounds; Free radicals; Oxidative processes; Oxidation; Cell damage; Cellular reactions; Cellular function; Author Keywords: Cadmium; Electron transfer chain; Reactive oxygen species; Mitochondria; Complex III; Q cycle; Free radicals
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
Issue of Publication
Free Radical Biology and Medicine
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division