Mitochondrial adenine nucleotide translocase is modified oxidatively during aging

Liang Jun Yan, Rajindar S. Sohal

Research output: Contribution to journalArticle

318 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)12896-12901
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number22
DOIs
Publication statusPublished - 27 Oct 1998

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