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 rather than a stochastic phenomenon. Oxidative damage to proteins in mitochondrial membranes in the flight muscles of the housefly, manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl antibodies. Adenine nucleotide translocase (ANT) was found to be the only protein in the mitochondrial membranes exhibiting a detectable age-associated increase in carbonyls. The age-related elevation in ANT carbonyl content was correlated with a corresponding loss in its functional activity. Senescent flies that had lost the ability to fly exhibited a relatively higher degree of ANT oxidation and a greater loss of functional activity than their cohorts of the same age that were 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 activity. In vitro treatment of mitochondria with a system that generated hydroxyl free radicals caused an increase in ANT carbonyl level and a decrease in ANT exchange activity. ANT was also the only mitochondrial membrane protein exhibiting adducts of the lipid peroxidation product 4-hydroxynonenal. Results of this study indicate that proteins in mitochondrial membranes are modified selectively during aging.
Yan
L J
LJ
Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.
Sohal
R S
RS
D000332:Aerobiosis; D000595:Amino Acid Sequence; D000818:Animals; D009033:Culicidae / Q000201:enzymology; D004330:Drosophila / Q000201:enzymology; D006793:Houseflies / Q000201:enzymology / Q000254:growth & development*; D007425:Intracellular Membranes / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010100:Oxygen; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000226:Mitochondrial ADP, ATP Translocases; D010100:Oxygen