MITOCHONDRIAL ADENINE-NUCLEOTIDE TRANSLOCASE IS MODIFIED OXIDATIVELY DURING AGING

The purpose of this study was to test the hypothesis that elevation in protein oxidative damage during the aging process is a targeted rathe r than a stochastic phenomenon. Oxidative damage to proteins in mitoch ondrial membranes in the flight muscles of the housefly, manifested as carbonyl modifications, was detected immunochemically with anti-dinit rophenyl antibodies. Adenine nucleotide translocase (ANT) was found to be the only protein in the mitochondrial membranes exhibiting a detec table age-associated increase in carbonyls. The age-related elevation in ANT carbonyl content was correlated with a corresponding loss in it s functional activity, Senescent flies that had lost the ability to fl y exhibited a relatively higher degree of ANT oxidation and a greater loss of functional activity than their cohorts of the same age that we re still able to fly. Exposure of flies to 100% oxygen resulted in an increase in the level of ANT carbonyl content and a loss in its activi ty. In vitro treatment of mitochondria,vith a system that generated hy droxyl free radicals caused an increase in ANT carbonyl level and a de crease in ANT exchange activity. ANT was also the only mitochondrial m embrane protein exhibiting adducts of the lipid peroxidation product 4 -hydroxynonenal, Results of this study indicate that proteins in mitoc hondrial membranes are modified selectively during aging.