Chromium(V) is produced upon reduction of chromate by mitochondrial electron transport chain complexes.
Incubation of chromate with isolated rat liver submitochondrial particles under anaerobic conditions in vitro results in reduction of chromium(VI) and formation of chromium(V). In the presence of NADH, submitochondrial particles (SMPs) were active in reducing chromate as shown by UV-vis spectroscopic studies, and forming a chromium(V) species which was detectable by electron paramagnetic resonance spectroscopy. In the presence of succinate, SMPs were less effective in reducing chromate and forming chromium(V) relative to their NADH-dependent activity. However, SMPs showed a higher rate of oxygen depletion with NADH as compared to succinate as substrate, suggesting that differences in the NADH-dependent versus succinate-dependent chromate-reductase activity of SMPs is probably due to differences in efficiency of electron donation by succinate and NADH. The use of specific electron transport chain inhibitors allowed the sites of chromium(VI) reduction and chromium(V) formation in SMPs to be determined. Rotenone, antimycin and cyanide all produced approximately 40% inhibition of the NADH-dependent chromate-reductase activity. Thus, complex I (NADH:ubiquinone oxidoreductase) appears to be responsible for the inhibitor-insensitive, and complex IV (ferrocytochrome c:oxygen oxidoreductase) for the inhibitor-sensitive NADH-dependent chromium(VI) reduction and chromium(V) formation. Cyanide and antimycin produced approximately 50% inhibition of the succinate-dependent chromate-reductase activity of SMPs, while no detectable inhibition was observed with rotenone. These results confirm the chromate-reductase activity of complex IV, and suggest that complex II (succinate:ubiquinone oxidoreductase) is responsible for the inhibitor-insensitive succinate-dependent chromate-reductase activity of SMPs. Since chromium(VI) is effectively metabolized by electron transport chain complexes of the mitochondrial inner membrane in vitro, and chromium(V) is formed as an intermediate in the process, mitochondria may play a role in chromium(VI) carcinogenesis.
Rossi
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SC
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755.
Wetterhahn
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KE
D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D002840:Chromates / Q000378:metabolism*; D002857:Chromium / Q000378:metabolism*; D003486:Cyanides / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008962:Models, Theoretical; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism*
D002840:Chromates; D003486:Cyanides; D012402:Rotenone; D002857:Chromium; C032456:antimycin; D000968:Antimycin A