Iron uncouples oxidative phosphorylation in brain mitochondria isolated from vitamin E-deficient rats

Abstract

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).

Increased expression of the F1Fo ATP synthase in response to iron in heart mitochondria

“…State 4 respiration, in particular, is a common consequence of uncoupling (6). Uncoupling often occurs in the presence of iron and consumes ATP (7). The present data obtained with iron overload are in good agreement with the estimates expected for uncoupling.…”

α-Tocopherol and Ascorbic Acid Administration Prevents the Impairment of Brain Energy Metabolism of Hyperargininemic Rats

“…Considering that antioxidant protection by α-tocopherol is crucial for an efficient mitochondrial respiration in the brain and that the cerebellum has low concentrations of this vitamin (Vatassery, 1998;Vatassery et al, 2004), the present work also evaluated whether the common antioxidants α-tocopherol plus ascorbic acid pretreatment could prevent the impairment of energy metabolism caused by Arg in Fig. 3.…”

“…In this context, α-tocopherol reduced the degeneration of hippocampal cells in animal models of cerebral ischemia (Hara et al, 1990) and enhanced the recovery of motor function after spinal cord injury (Anderson et al, 1988). More recently it has been suggested that α-tocopherol may have a specific role in maintaining oxidative phosphorylation (Vatassery et al, 2004) and that α-tocopherol plus ascorbic acid administration prevents the reduction of Na + , K + -ATPase and acetylcholinesterase activities caused by Arg (Bavaresco et al, 2002;Wyse et al, 2004).…”

Vitamin E prevents hypobaric hypoxia-induced mitochondrial dysfunction in skeletal muscle

“…Levels of vitamin E were measured by HPLC as described by Vatassery et al [22]. Briefly, 2 ml of ethanol containing 0.025 % (w/v) BHT (butylated hydroxytoluene) and 0.1 ml of 30 % (w/v) ascorbate was added to 100 µl of mitochondrial suspension.…”