Ferrous-iron induces lipid peroxidation with little damage to energy transduction in mitochondria.
Addition of ferrous sulfate, but not ferric chloride, in micromolar concentrations to rat liver mitochondria induced high rates of consumption of oxygen. The oxygen consumed was several times in excess of the reducing capacity of ferrous-iron (O:Fe ratios 5-8). This occurred in the absence of NADPH or any exogenous oxidizable substrate. The reaction terminated on oxidation of ferrous ions. Malondialdehyde (MDA), measured as thiobarbituric acid-reacting material, was produced indicating peroxidation of lipids. The ratio of O2:MDA was about 4:1. Pretreatment of mitochondria with ferrous sulfate decreased the rate of oxidation (state 3) with glutamate (+ malate) as the substrate by about 40% but caused little damage to energy transduction process as represented by ratios of ADP:O and respiratory control, as well as calcium-stimulated oxygen uptake and energy-dependent uptake of [45Ca]-calcium. Addition of succinate or ubiquinone decreased ferrous iron-induced lipid peroxidation in intact mitochondria. In frozen-thawed mitochondria, addition of succinate enhanced lipid peroxidation whereas ubiquinone had little effect. These results suggest that ferrous-iron can cause peroxidation of mitochondrial lipids without affecting the energy transduction systems, and that succinate and ubiquinone can offer protection from damage due to such ferrous-iron released from the stores within the cells.
Shivaswamy
V
V
Department of Biochemistry, Indian Institute of Science, Bangalore.
Kurup
C K
CK
Ramasarma
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002712:Chlorides; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008930:Mitochondria, Liver / Q000187:drug effects*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013386:Succinates / Q000494:pharmacology; D019802:Succinic Acid; D014451:Ubiquinone / Q000494:pharmacology
D002712:Chlorides; D005290:Ferric Compounds; D005296:Ferrous Compounds; D013386:Succinates; D014451:Ubiquinone; C020748:ferrous sulfate; D008315:Malondialdehyde; D019802:Succinic Acid; D002118:Calcium; C024555:ferric chloride