Oxidative stress in cardiac mitochondria caused by copper deficiency may be insufficient to damage mitochondrial proteins

Abstract

Copper (Cu) deficiency may promote the generation of reactive oxygen species (ROS) by the mitochondrial electron transport chain through inhibition of cytochrome c oxidase (CCO) and increased reduction of respiratory complexes upstream from CCO. In the present study, respiration, H2O2 production and aconitase activity were measured in isolated heart mitochondria from weanling rats fed diets that were either deficient (CuD, <1ppm Cu), marginally deficient (CuM, 1.5 ppm Cu) or adequate (CuA, 6 ppm Cu) in Cu for 8 weeks. State 4 respiration (μmole O2 ·min−1 ·mg−1) in CuD rats (2.81±0.71) was lower (P<0.05) than in CuM (3.74±0.88) or CuA rats (3.72±0.78). H2O2 production (nmol · min−1 ·mg−1) in the presence of rotenone was marginally higher (p=0.07) in CuD rats (11.2±4.1) than in CuM rats (8.5±2.4) or CuA rats (8.2±2.6). However, aconitase activity (mU ·mg−1) was higher (P<0.05) in CuD rats (58.5±12.5) than in CuM (25.8±7.0) or CuA rats (28.4±9.3). Aconitase is readily inactivated by ROS and these findings suggest that even though severe Cu deficiency impairs mitochondrial function, mitochondrial oxidative stress is not elevated to a level that leads to oxidative inactivation of susceptible mitochondrial enzymes. Enhancement of aconitase activity may reflect enhanced TCA cycle activity for maintenance of cardiac energy production during Cu deficiency.Supported by USDA‐ARS