Iron uncouples oxidative phosphorylation in brain mitochondria isolated from vitamin E-deficient rats.
Few, if any, studies have examined the effect of vitamin E deficiency on brain mitochondrial oxidative phosphorylation. The latter was studied using brain mitochondria isolated from control and vitamin E-deficient rats (13 months of deficiency) after exposure to iron, an inducer of oxidative stress. Mitochondria were treated with iron (2 to 50 microM) added as ferrous ammonium sulfate. Rates of state 3 and state 4 respiration, respiratory control ratios, and ADP/O ratios were not affected by vitamin E deficiency alone. However, iron uncoupled oxidative phosphorylation in vitamin E-deficient mitochondria, but not in controls. In vitamin E-deficient mitochondria, iron decreased ADP/O ratios and markedly stimulated state 4 respiration; iron had only a modest effect on these parameters in control mitochondria. Thus, vitamin E may have an important role in sustaining oxidative phosphorylation. Low concentrations of iron (2 to 5 microM) oxidized mitochondrial tocopherol that exists in two pools. The release of iron in brain may impair oxidative phosphorylation, which would be exacerbated by vitamin E deficiency. The results are important for understanding the pathogenesis of human brain disorders known to be associated with abnormalities in mitochondrial function as well as iron homeostasis (e.g., Parkinson's disease).
Vatassery
Govind T
GT
Reserch Service and GRECC, VA Medical Center, Minneapolis, MN 55417, USA. vatas001@tc.umn.edu
DeMaster
Eugene G
EG
Lai
James C K
JC
Smith
W Ed
WE
Quach
Hung T
HT
D000818:Animals; D001921:Brain / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D014475:Uncoupling Agents / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000378:metabolism / Q000494:pharmacology
D014475:Uncoupling Agents; D007501:Iron; D024502:alpha-Tocopherol