Selectivity of protein oxidative damage during aging in Drosophila melanogaster

Abstract

The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative 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 to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted 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 oxidative stress causes age-associated losses in specific biochemical functions.

OXIDIZED LIPIDS DID NOT REDUCE LIFESPAN IN THE FRUIT FLY, Drosophila melanogaster

“…Increasing level of oxidatively modified proteins during aging was found in numerous studies (Das et al., ; Levine et al., ; Clancy and Birdsall, ). The absence of age‐related changes in levels of PC in the current study does not confirm results of these studies.…”

“…However, it is known that protein carbonylation profile can be species specific (Clancy and Birdsall, ). It was also shown that certain proteins, like mitochondrial aconitase, are particularly susceptible to oxidative modification during aging in D. melanogaster (Das et al., ). In our previous studies, we found that Drosophila aconitase was indeed very susceptible to the influence of reagents producing nitric oxide (Lozinsky et al., , ).…”

“…On the other hand, it is not entirely clear whether oxidative modification of specific molecules play a particular role in aging. It was demonstrated that not all proteins are equally susceptible to oxidation (Cabiscol et al., ; Das et al., ; Lushchak and Gospodaryov, ). In some cases, this oxidation can either be reversible (Grant, ) and/or reparable (Davies, ).…”

Aging Enhances Indirect Flight Muscle Fiber Performance yet Decreases Flight Ability in Drosophila

“…Additionally, reduced ATP availability reduces myosin kinetics in isolated fibers (41), and reduced myosin kinetics leads to decreases in wingbeat frequency (42). In further support of this hypothesis, microarray studies show that genes involved in energy metabolism are downregulated with age in flies (43), and biochemical studies show reduced mitochondrial enzyme activity (8) and respiration (9) with age in flies.…”

“…Although human skeletal and Drosophila indirect flight muscle (IFM) show major differences in muscle fiber type, regenerative ability, and innervation, both sets of muscles are postmitotic and rely upon similar contraction and energy supply mechanisms. Drosophila IFM, like human muscle, have age-related decrements in functional performance (reviewed by Grotewiel et al (6)), protein expression (7), and mitochondrial function (8,9), as well as age-related changes in gene expression (10). Notably, flies provide an excellent model system for aging research due to their short life span, ease of maintenance and powerful genetics; in addition, in-depth knowledge of numerous aging processes is available due to the multitude of studies performed in this species.…”