Selectivity of protein oxidative damage during aging in Drosophila melanogaster

The purpose of the present study was to determine whether oxidation of vari ous proteins during the aging process occurs selectively or randomly, and w hether the same proteins are damaged in different species. Protein oxidativ e damage to the proteins, present in the matrix of mitochondria in the flig ht muscles of Drosophila melanogaster and manifested as carbonyl modificati ons, was detected immunochemically with anti-dinitrophenyl-group antibodies . Aconitase was found to be the only protein in the mitochondrial matrix th at exhibited an age-associated increase in carbonylation. The accrual of ox idative damage was accompanied by an approx. 50% loss in aconitase activity . An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure t o 100% ambient oxygen showed that aconitase was highly susceptible to under go oxidative damage and loss of activity under oxidative stress. Administra tion of fluoroacetate, a competitive inhibitor of aconitase activity, resul ted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidativ e stress causes age-associated losses in specific biochemical functions.